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|342 posts found
Originally posted by SpottyGekko
Are sub-locked game designers stupid and just design their games willy nilly? Are you going to posit that they don't analyze metrics and design games around gear treadmills, time sinks, and mechanics to make you sub longer?
Again, I notice that sub-locked proponents like to use really vague references to un-named sub-free games to make their arguments. If a game has a bad model and mechanic then name it. Stop saying all games do this when one game does that. If there is a horrible setup then lets discuss that.
If I get to the point in a game, it doesn't matter whether the game is sub-locked or sub-free, where progression stops or becomes "unfun" then I will probably stop playing. If I start to play a sub-free game and I look in the cash shop and experience the game mechanics and decide that I don't like them, then I move on. If I get to a place in a sub-locked game where I have to do things I don't like to progress then I move on.
It's really really simple. If a game has bad mechanics then don't play it. Play fun games. If you like to rent your games then play fun sub-locked games. If you don't then play fun sub-free games.
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Spotlight Poster
Joined: 3/31/09
Mtibbs1989, we aren't on the same page.
You: "You can never can be better than the big spender"
Me: "You are never even be at the average because of not spending more"
Apprentice Member
Joined: 3/10/04
Be Brief, Be Bright... Be Gone.
Originally posted by mmoguy43
Me: Are you having fun? Yes, then who cares. No; drop the game.
Me: You specifically state multi-boxing, which exists today. F2p does not change that. Therefore it is a non issue in a f2p vs p2p comparison.
Quit worrying about other players in a game and just play.
Advanced Member
Joined: 12/21/07
Originally posted by mmoguy43
None of that is important if you are playing pve, and play for fun, instead of epleen. Do you really need to be "above average" in a game where achievements are just illusions anyway?
Novice Member
Joined: 12/18/11
Originally posted by Quizzical
As you seem fairly "learn-ed", based on the countless totaly positive posts I see you make in the tech forum, I can assume that you know of "weasel words"? In short, if you are unaware, these are words used most often by advertisers and politians, to skew meaning. A prime example would be a generic product claiming to be "virutally" like its name brand counterpart. SImply put, we all know that "virtually" means, not the same. Yet countless consumers grab the generic and proclaim "It is the SAME as its name brand counterpart!". Total win for the advertiser. I have come to see "F2P" as the same kind of situation. Sure, you can download, install, and "play" for free...but as you point out, they make it very inconvienant, creating artificial "need" for cash shop items.
Is it "evil", "lies", "trickery"? Maybe. Who knows? For me it is another example of the reasons I try to be an "educated skeptic consumer". Sometimes it is hard to do since they want to "hook" you into playing before you know all the facts. Lucky for us there are countless forums and such to fill our heads with all the info we need. (A discussion for another thread on the quality of this info).
I do however support discussions of this sort. When I see them I try to participate in a positive manner. I do this in the hopes of spreading knowledge. SInce many of these topics bleed into everyday life and do not just pertain to gaming. My hats off to you sir for starting this thread.
Novice Member
Joined: 8/20/03
It seems to me that most F2P devs are aware of the outrage and anger caused by nickle and dime mechanics which is why they design the games to be short lived, shallow experiences. Between the player mill (old out, new in, in rapid succession) and the cheap development, running a game into the ground and replacing it with another cheap thrill is much easier than a 300mil behemoth title.
I mean, look at Aeria games site, 22 F2P titles alone, and likely that a few of them won't make it through summer. How many sub-based devs could carry that many titles?
Anyway, I've yet to see a free to play title that encouraged long term time investment, and while they may be replacing sub models in popularity, I don't think they're intended to replace sub-games in playstyle.
I think subs still have a chance and a community but has lost a lot of steam from the corporate side. Free to play is simply a trending cash grab that is establishing its own market and will hopefully take a chunk of the 'business ethic' out of the sub based genre and set us back toward the days when a sub carried weight in the eyes of the devs. :p
(I'm dreaming again right?)
Elite Member
Joined: 7/02/11
Just the fact alone that F2P games are really embracing the whole pay for your interface options piecemeal is a huge turnoff for me. As is the inability in some games to expand your storage space other than through the cash shop. Whats even worse is that some companies are doing this by character and not by account. The costs and the irritation are killing this aspect of the genre for me.
Advanced Member
Joined: 12/21/07
Originally posted by Popori
Originally posted by Quizzical
And what are those formulas going to tell you, if they're up to date? Are you going to understand how to build a character? Is it going to tell you if the game is fair?
Rift is a good example of a sub-locked game that has dramatically changed some core mechanics over the last two years. It's not the same game I bought into and paid a bunch of money for. The alternate advancement system has been radically altered. All falling damage has been removed. Gear progression has been altered since Storm Legion. Faction interaction has dramatically changed since launch.
Even if you can look something up can you interepret it? If someone is confused by the differences between "P2P" and "F2P" are they going to understand and make good decisions about combat formulas? In Rift the following is true as of a year ago (that's the datetime stamp on the wiki page):
1 point of resistance equals 0.1% chance to resist spells of that damage type.
1 point of resistance equals .05% reduction in damage of that type.
Exactly what is someone going to do with that knowledge? Are you going to go in and stack resistance? Or is direct armour mitigation more effective? Is building for evasion more prudent? You never really know that stuff until you get in and experience the game and test the mechanics yourself. The best you may be able to do is read raid parsing online and try to extrapolate that to every encounter type in the game.
Every company, regardless of the revenue model, is under continual pressure to generate more revenue. Some of those changes in Rift were a direct result of trying to pull in a broader cross section of the raid demographic. The pressure to sell more in an item mall doesn't mean the first way that will happen is going to be selling super power items. That may be true in some games, but that is where someone makes an individual evaluation and either accepts it or moves on.
Spotlight Poster
Joined: 3/31/09
Originally posted by nariusseldon
What if I play for grouping, pvp, and the community? It could be imporant in that regard. Yes, I always need to start at atleast the average even if merely play for fun.
Elite Member
Joined: 7/02/11
Originally posted by Torvaldr
What makes you think we are playing these F2P monstrosities? Something tells me I will not be waiting in vain for Elder Scrolls which is most likely going to have a subscription model. Currently subscribed to Rift in the meantime.
Novice Member
Joined: 2/16/11
I'll kick your a**e so hard, you could build a swimming pool in the footprint!
Originally posted by Quizzical
Taking the term litterally, then no. They'll keep using it because it sounds great to a potential customer and is true to a point.
All of those games you can download and play for free. 'Free 2 Play', is a buzzword phrase like, 'dynamic content', they imply something good but don't actually describe what that fully entails.
That's how marketing works, it's lures you to try something and it's job is to, 'sell', a lifetyle, product, whatever, as positively as possible, in the quickest timeframe, without acknowledging any questionable aspects. Until they find a better term, expect to see it in use for a while...
This looks like a job for....The Riviera Kid!
Elite Member
Joined: 9/26/04
Originally posted by Torvaldr
Yours is a popular "rebuttal" against the argument of F2P Cash Shop manipulation.
But it's flawed.
It's flawed because both P2P and F2P game designs need to keep people playing. Regardless of the design, if the player is not playing the game, there is no chance at all that he will be spending money on it.
In fact, the "grind-by-design" in most F2P games is far, far worse than in P2P games, because the grind has to be made unpalatable enough so that most people will opt for straight-out purchases. A P2P design cannot do that, because there's no "easy-way-out" in a P2P game.
If your P2P grind is more than the average player can bear, you will lose the player.
If your F2P grind is more than the average player can bear, you have a huge group of potential Cash Shop customers !
Novice Member
Joined: 2/27/08
Originally posted by Falstaff
As long as you're not treating MMOs like personal dick-waving machines, you can play for free. It's the hyper-competitive assholes who have to be #1 and live to show off that have issues, and they should.
Played: UO, EQ, WoW, DDO, SWG, AO, CoH, EvE, TR, AoC, GW, GA, Aion, Allods, lots more
Novice Member
Joined: 2/27/08
Originally posted by ShakyMo
How do they pick your pockets, you have to decide to enter your credit card number, they can't do it without your permission.
It's not them picking your pockets, it's you having no self-control.
Played: UO, EQ, WoW, DDO, SWG, AO, CoH, EvE, TR, AoC, GW, GA, Aion, Allods, lots more
Apprentice Member
Joined: 10/04/12
I don't feel cripped in PoE, TERA, Dota2, TF2 etc.
DAoC - Excalibur & Camlann
Originally posted by Vorthanion
Wait, that's news to me. Are ALL F2P games "really embracing the whole pay for your interface options piecemeal" deal? I guess I'm going have to spend a lot of money in GW2, Tera, STO, GW, TSW, LotRO, and EQ2 buying those interface options. I didn't realize the entire industry acted as a single unit.
It must suck for the WoW players when Rift homogenized alternate advancment. Because you know, all p2p games make the same changes too.
Or were you taking one example and applying it to the entire industry?
Let's say you need to expand your storage through the cash shop (and I'll use real world examples). In Tera a bank slot (there are 4 total and you start with 1) costs $5 or you can buy all 3 for $14. In STO a slot is $10. I find it odd that spending $15 or less on a character unlock you can always use is less appealing than renting access to a character for $15 a month. If you're spending the same as a subscription why does it matter?
Why is it okay for a subscription to cost an average of $150 - $220 per year for rented access but if you spend the same amount on a sub-free game to unlock account features or gameplay then it's a cost gouge that kills that aspect of the genre for you? I have yet to spend as much in a sub-free game as a sub-locked game.
Apprentice Member
Joined: 4/20/13
The title is as true as it is long, at least for 95% of F2P games.
Hard Core Member
Joined: 3/20/13
Originally posted by Quizzical
This is why I don't like F2P or B2P? Even with games like GW2, you never know what changes might be made to the cash shop and the items available in it. All it takes is a bad quarter or two financially, and a company will do most anything to increase revenue.....
James T. Kirk: All she's got isn't good enough! What else ya got?
Novice Member
Joined: 8/20/03
Originally posted by nariusseldon
I haven't seen much proof that F2P has been stealing customers from sub games, if anything it seems that more people are joining the market thanks to F2P.
The popularity of F2P won't just nullify the demand for what sub games currently offer (or were supposed to be). So, until F2P can cover that gap I don't see them conquering the market outright (and I don't see them making any attempt to fill that gap).
As you stated, F2P titles will continue to become more short-term, and without commitment, until the players that are not looking for that turn elsewhere. Maybe it will be subs, maybe it will be some F2P mutant that offers something that F2P currently isn't designed for - I can't pretend to know.


text:
Lasse Schone notched the winner six minutes after the re-start as Ajax claimed the three points to climb above the Hoops in Group H.
But Celtic's Beram Kayal and Anthony Stokes failed with opportunities to score, while James Forrest should have picked out Stokes in the 57th minute as he raced down the right but managed to hit Joel Veltman, the only Ajax outfield player back.
Lennon's side must now beat AC Milan at Celtic Park later this month to have any realistic hope of qualifying ahead of their last game against Barcelona.
He told Sky Sports: I thought we were poor first half, I thought we were a lot better second half.
"The goal came at a time when we were just starting to get a foothold in the game. That's a poor goal from our point of view.
"But we had chances second half, particularly the two v one with Jamesie breaking - you're thinking it was a great opportunity and that might have just changed the course of the game.
"But I thought we were second best first half and some players will have regrets about their performance tonight because they weren't anywhere near their best."
He added: "We've left ourselves a lot to do. The last game, at the Nou Camp, is not the easiest place to go.
"But there's still a lot to play for in the group."

subset: commoncrawl


text:
$23,553 – $26,895 Invoice
19 / 26 MPG City/Hwy
Enter your information and a representative will contact you for this 2007 Buick Rendezvous !
What's New
Four-wheel anti-lock disc brakes and Turn-by-Turn Navigation via a 1-year subscription to OnStar's Directions & Connections have been added to the standard features list for the 2007 Rendezvous. CX models have been bolstered with several new options: a trailer hitch, satellite radio, rear audio controls, and removable second-row captain's seats. Traction control-equipped models also feature a tire-pressure-monitoring system and Driver Information Center.
Originally introduced in 2002, the Rendezvous remains Buick's premium crossover sport utility vehicle (SUV) for 2007. Buick's intent in designing the Rendezvous was to create a vehicle that combined the best elements of a minivan, a luxury car, and an SUV. This marks the Rendezvous' last year of production, however, it makes way for the 2008 Enclave, which will represent Buick's next-generation of luxury crossover vehicles. As part of the Rendezvous' phase out, it only offers CX and CXL trim levels this year; the Plus editions have been eliminated. To help compensate for the former up-level Plus models, base 2007 CX models now offer the added options listed above in "What's New"
Capable of carrying up to 7 passengers with the optional fold-flat third-row seat, the Rendezvous shares the same basic unibody platform as the Buick Terraza minivan. Available in front-wheel drive only (all-wheel drive has been dropped for 2007), the Rendezvous offers a traction control option on CX models (it's standard on the CXL). An automatic rear-level control system that employs the use of airbladders around the shock absorbers to improve ride and handling when towing or carrying loads is included in an optional trailering package. The onboard compressor can be used to inflate tires and other items. Equipped with the trailering package, the Rendezvous is rated to tow up to 3,500 pounds.
Sole power for the Rendezvous is a 196-hp, 3.5-liter V-6 engine; the beefier 242-hp, 3.6-liter V-6 offered last year is not available on 2007 models. The engine is mated to an electronically-controlled 4-speed automatic transmission with overdrive and torque converter clutch. And like all Buick models, the Rendezvous comes standard with QuietTuning sound-deadening enhancements for a quieter than average ride, and is covered by GM's new 5-year/100,000-mile limited powertrain warranty.
The Competition
The Buick Rendezvous competes in the Midsize Crossover Utility Vehicle (CUV) segment, which consists of 13 models. Buyers in this segment look for comfort, reliability, and quality, according to the J.D. Power and Associates 2006 Avoider StudySM and the Escaped Shopper Study.SM
The top sellers in the segment during calendar year 2006, according to the J.D. Power and Associates Sales Report,SM were the Toyota Highlander (129,794 units sold), Nissan Murano (81,362), and Chrysler Pacifica (78,243). The Buick Rendezvous sold 45,954 units in 2006, a decrease of 24.2 percent compared to the previous year. Other models offered in the Midsize CUV segment include the Ford Freestyle, Subaru B9 Tribeca, and Hyundai Santa Fe. Joining the segment in 2007 are the Ford Edge, GMC Acadia, Mazda CX-9, and Saturn Outlook.
|City/Hwy MPG
|4 speed automatic
|195-hp / 3.5L 6-cyl
|4 speed automatic
|195-hp / 3.5L 6-cyl
$27,635–$38,385 Base MSRP
$24,677–$34,275 Invoice
16/19 MPG City/Hwy
$24,880–$32,210 Base MSRP
$22,141–$28,667 Invoice
18/24 MPG City/Hwy
$32,490–$36,550 Base MSRP
$29,076–$32,744 Invoice
31/27 MPG City/Hwy
$27,370–$34,005 Base MSRP
$25,910–$32,014 Invoice
15/21 MPG City/Hwy


text:
Visitor Information
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The University of Maryland Libraries provide access to many sources of information useful for the study of Italian Renaissance art. This session will offer an overview of research skills, library services and relevant resources including the Libraries' online Catalog, and subject-specific databases available through Research Port.
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text:
Apple QuickTime ActiveX Control Clear Method Use-After-Free (CVE-2012-3754)
|Check Point Reference:
|Date Published:
|Apple Advisory 56438
|Industry Reference(s):
|Protection Provided by:
Security Gateway
Who is Vulnerable?
Apple QuickTime prior to 7.7.3
|Vulnerability Description
A use-after-free vulnerability has been reported in Apple QuickTime's ActiveX control.
Vulnerability Details
The vulnerability is due to an error while handling a certain method. A remote attacker can exploit this vulnerability by enticing a target user to open a specially crafted web page using Internet Explorer. Successful exploitation could lead to arbitrary code execution in the security context of the logged in user.
Protection Overview
IPS will detect and block attempts to exploit this vulnerability.
In order for the protection to be activated, update your product to the latest update. For information on how to update , go to SBP-2006-05, Protection tab and select the version of your choice.
To configure the defense, select your product from the list below and follow the related protection steps.
Security Gateway R75 / R71 / R70
How Can I Protect My Network?
- In the IPS tab, click Protections and find the Apple QuickTime ActiveX Control Clear Method Use After Free protection using the Search tool and Edit the protection's settings.
- Install policy on all modules.
How Do I Know if My Network is Under Attack?
SmartView Tracker will log the following entries:
Attack Name: Apple QuickTime Protection Violation
Attack Information: Apple QuickTime ActiveX Control Clear Method Use After Free


text:
Cameron Ling a 189cm, 94kg midfielder made his AFL debut in 2000. He was recruited from Geelong U18 and now plays for the Geelong Cats. He was born in 1981.
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Former premiership captain Cameron Ling believes Melbourne can bounce back quickly from their Round 1 disaster if they get their attitude right ahead of Saturday's clash against the Bombers.
In his first exclusive column for Sportal.com.au, Cameron Ling reveals that he thinks Fremantle are in for a huge 2013, while he names the player he says will win the Brownlow Medal.
Cameron Ling bowed out of football the way every player dreams of, as a premiership captain for the team he supported his whole life.
Cameron Ling has revealed he'd been contemplating retirement for the past year but only made up his mind once and for all in the wake of last Saturday's premiership victory over Collingwood.
Geelong premiership captain Cameron Ling has announced his retirement from AFL football effective immediately.
Geelong premiership captain Cameron Ling is expected to announce his retirement on Wednesday afternoon.
Geelong captain Cameron Ling says emerging trio Daniel Menzel, Allen Christensen and Mitch Duncan will play important roles in the club's finals campaign.
Geelong captain Cameron Ling is among four players set to return for the unbeaten Cats' away clash with Gold Coast on Saturday night.
Geelong captain Cameron Ling is in serious doubt for Saturday's clash with North Melbourne with the recurrence of a hamstring strain.
Captain Cameron Ling believes evolution, rather than revolution, under new coach Chris Scott is the best way to regenerate Geelong, with the Cats unlikely to make wholesale changes to either personnel...
Only registered members can share their thoughts. So come on! Join the Footy Post community today (totally free) and do things you never thought possible.


text:
The method of imaging a spatial distribution of photon emitters, the method includes producing an image with a resolution of at most about 180 microns using an imaging device including a detector and a coded aperture, wherein a photon emitted from the photon emitter has an energy of at most about 35 keV (5.6×10−15 J). Further provided is an imaging device for imaging a distribution of photons having energies of at most about 35 keV (5.6×10−15 J), which includes a coded aperture comprising a mask pattern having a plurality of holes, wherein the coded aperture is adapted to provide a resolution of at most about 180 micron, a detector on which a raw image is projected through the coded aperture; and a decoder that receives the raw image from the detector and produces an image having a resolution of at most about 180 micron.
1. A method of imaging a spatial distribution of photon emitters, the method comprising producing an image with a resolution of at most about 180 microns using an imaging device comprising a detector and a coded aperture, wherein a photon emitted from the photon emitter has an energy of at most about 35 keV (5.6×10−15 J).
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14. An imaging device for imaging a distribution of photons having energies of at most about 35 keV (5.6×10−15 J), said imaging device comprising:
a coded aperture comprising a mask pattern having a plurality of holes, wherein the coded aperture is adapted to provide a resolution of at most about 180 micron;
a detector on which a raw image is projected through the coded aperture; and
a decoder that receives the raw image from the detector and produces an image having a resolution of at most about 180 micron
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This application claims a benefit of U.S. Provisional Application No. 60/466,657 filed on Apr, 30, 2003, titled 10-MUM RESOLUTION IMAGER FOR SOFT X-RAY EMITTERS, which is incorporated herein in its entirety.
This research was supported in part by U.S. Government funds (Grant No. 1 R21 EB002610-01 from the National Institute of Biomedical Imaging and Bioengineering of the NfH), and the U.S. Government may therefore have certain rights in the invention.
1. Field of the Invention
This invention relates to imaging of radiation-emitting objects and, more particularly, it relates to imaging of radioactive sources with a resolution of about 10 micron, i.e. on the same scale as individual human somatic cells.
2. Description of Related Art
Radionuclide imaging is an established technique capable of providing functional information at the molecular level with both high specificity and high sensitivity. The technique is based on labeling molecules with a radioactive atom before their release in the system under study. The spatial distribution of the molecules can then be followed in time by imaging the location of the emitted radiation. A large number of isotopes can be imaged. The broadest classification is their separation in gamma and positron emitters, the former is at the basis of single photon emission methods (such as scintigraphy and tomography or SPET) and the latter is used in Positron Emission Tomography (PET).
Recent interest in small animal imaging increased the emphasis on the question of the ultimate resolution limit of these instruments. Further improvement of state-of-the-art PET systems (see, for example, Tai et al., "MicroPET II: An Ultra-high Resolution Small Animal PET System," IEEE 2002 Medical Imaging Conference Proceedings) some of which are capable of 1 mm resolution (see Jeavons et al., "A 3d HIDAC-PET with sub-millimetre resolution for imaging small animals," IEEE Transactions on Nuclear Science, 46,468-473, 1999) will have to face increasing instrumentation costs and eventually fundamental physical limits such as finite positron range and photon non-colinearity. Single-photon imagers with sub-millimeter resolution have already been designed and built both with dedicated detectors and as adaptations of pre-existing clinical-type equipment (see MacDonald et al., "Pinhole SPECT of Mice Using the LumaGEM Gamma Camera," IEEE Transactions on Nuclear Science, 48,3, 830-836,2001; and Acton et al., "Ultra-high resolution single photon emission tomography imaging of the mouse striatum," European Journal of Nuclear Medicine, 29, 3, 446, 2002). These systems are based on the combination of a position-sensitive detector with some absorptive collimation optics to associate each detected event with an emission location (see J. A. Sorensen and M. E. Phelps, Physics in Nuclear Medicine, Grune and Stratton, Orlando, 1987). Their performance limit is set by a trade-off among many parameters, the most notable of which are usually resolution, sensitivity and Field of View (FoV). Coded aperture imaging has been proposed in the past as a means for improving the spatial resolution, sensitivity, and signal-to-noise ratio (SNR) of images formed by x-ray or gamma ray radiation (see Caroli et al., "Coded aperture imaging in x- and gamma-ray astronomy," Space Science Reviews, 45,349-403,1987;and G. K. Skinner, "Imaging with coded aperture masks," Nuclear Instruments and Methods in Physics Research, 221, 33-40, 1984). For many imaging applications, coded aperture cameras have proven advantageous relative to other candidate systems, including the single pinhole camera and collimator systems. In coded aperture imaging, radiation from the object to be imaged is projected through the coded aperture mask and onto a position-sensitive detector. The coded aperture mask is an arrangement of many pinholes in particular patterns. The raw signal from the detector does not reflect a directly recognizable image, but instead represents the signal from the object that has been modulated or encoded by the aperture pattern. The recorded signal can then be digitally or optically processed to extract a reconstructed image of the object (see Accorsi et al., "Optimal coded aperture patterns for improved SNR in nuclear medicine imaging," Nuclear Instruments and Methods in Physics Research, 474(3): 273-284, 2001 and references therein).
The following equations regulate interdependences between resolution, sensitivity and Field of View (FoV) for a pinhole:
For an ideal (infinitely small) pinhole, w=0, and the equation (1) shows that resolution is limited by the intrinsic resolution of the detector. For a perfect detector (FWHMi=0), the equation (1) shows that resolution is proportional to w. On the other hand, the equation (2) shows that the sensitivity g is proportional to w2, so that better (i.e. lower) resolution leads to worse sensitivity, unless a is reduced. However, the equation (3) shows that for given D and b, a reduction in a implies a reduction in FoV. Furthermore, as discussed below, practical constraints may pose a limit on the minimum a.
The equation (1) also shows that resolution better than the intrinsic resolution of the detector can be obtained if a magnifying geometry (m>1, i.e. b>a) is used (see D. A. Weber and M. Ivanovic, "Pinhole SPECT: Ultra-high-resolution imaging for small animal studies," Journal of Nuclear Medicine, 36, 12, 2287-2289, 1995). To achieve good resolution, parallel-hole collimators, for which m=1 and whose resolution and sensitivity can be calculated with similar equations (see J. A. Sorensen and M. E. Phelps, supra), must be coupled with research-type detectors having outstanding intrinsic resolution. For example, Kastis et al. have coupled a tungsten collimator with a 380 μm-pitch CZT detector (see Gamma-ray imaging using a CdZnTe pixel array and a high-resolution, parallel-hole collimator, IEEE Transactions on Nuclear Science, 47, 6, 1923-1927, 2000). Magnification is achieved more readily with pinholes than with converging collimators. A representative pinhole system designed for 99mTc photons (140 keV) uses a 1-mm diameter pinhole, a=3.3 cm and b=26 cm (m=7.9) with D=30 cm (see Habaken et al.,"Evaluation of High-Resolution Pinhole SPECT Using a Small Rotating Animal," Journal of Nuclear Medicine, 42, 1863-1869, 2001). With these numbers, the equations above show a geometric resolution of 1.1 mm (1.2 mm system resolution assuming 3.7 mm FWHMi, the intrinsic resolution specified for a Siemens E-Cam) and a sensitivity of 5.7×10−5 (57 cps/MBq) over a FoV of 3.8 cm, which compare to an experimental system resolution of 1.3 mm and sensitivity of 48.5 cps/MBq.
To further improve resolution two problems must be faced: pinhole penetration and sensitivity. In fact, if pinholes were cut in an ideal material perfectly opaque to gamma rays, the material could be infinitely thin and the FoV would only be limited by the size of the detector. However, in practice, materials have a finite absorption coefficient μ and some finite thickness must be used. To maintain a large FoV, pinholes seldom have a straight axial profile, but rather have a 'knife-edge' to pass photons with a larger acceptance angle t Penetration at the edge is more pronounced, and resolution is reduced because the pinhole appears to photons to be larger than its actual size. The effect has been quantified by defining the effective diameter we in the equation (4):
Even if this definition was originally based on sensitivity considerations, the effective diameter is commonly used in place of the physical diameter w in the equation (1) to calculate resolution (see M. F. Smith and R. J. Jaszczak, The effect of gamma ray penetration on angle-dependent sensitivity for pinhole collimation in nuclear medicine, Medical Physics, 24, 11, 1701-1708, 1997; and Jaszczak et al., Pinhole collimation camera for ultra-high resolution, small field of view SPECT, Physics in Medicine and Biology, 39, 425-437, 1994).
The equation (4) shows that, when penetration is accounted for, even a physically closed pinhole (w=0) leads to finite geometric resolution. For example, for 140 keV and an α=100° pinhole made of gold, we=0.56 mm. This result depends only on the attenuation coefficient (and hence on the energy of the photons) and the acceptance angle.
Two approaches have historically been proposed to overcome the well-known limit of sensitivity in pinhole imaging while maintaining fundamental design parameters such as detector dimensions, FoV and resolution. Both rely on increasing the number of pinholes used, to which sensitivity is in first approximation proportional. A multiple pinhole system is one in which the different pinholes cast projections of the object on distinct parts of the detector. A coded aperture system is one in which the projections could overlap. A disadvantage of multiple pinholes is that their number and magnification are limited to keep projections separated. A disadvantage of coded apertures is that the increased sensitivity does not always translate in increased Signal-to-Noise Ratio (SNR). The basics of coded aperture imaging will now be described with the goal of analyzing in more detail the conditions under which it provides better SNR than a pinhole.
Coded aperture imaging was originally developed to improve the SNR of X-ray astronomy instrumentation (Caroli et al., supra; and G. K. Skinner, supra) and was successively applied to other fields, such as physics (Fenimore et al., "Uniformly redundant array imaging of laser driven compressions: preliminary results," Applied Optics, 18, 945-947, 1979; and Chen et al., "Three-dimensional reconstruction of laser-irradiated targets using URA coded aperture cameras," Optics Communications, 71, 249-255, 1989) and medicine (J. S. Fleming and B. A. Goddard, "An evaluation of techniques for stationary coded aperture three-dimensional imaging in nuclear medicine," Nuclear Instruments and Methods in Physics Research, 221, 242-246, 1984; Liu et al., "A novel geometry for SPECT imaging associated with-the EM-type blind deconvolution method," IEEE Transactions on Nuclear Science, NS-45, 2095-2101, 1998; H. H. Barrett, "Fresnel zone plate imaging in nuclear medicine," Journal of Nuclear Medicine, 13, 382-385, 1972; Koral et al., "Thyroid scintigraphy with time-coded aperture," Journal of Nuclear Medicine, 20,345-349,1979; and Rogers et al., "Coded-Aperture imaging ofthe heart," Journal of Nuclear Medicine, 21, 371-378, 1980). The fundamental idea is to increase signal throughput by opening multiple pinholes, which are kept small to preserve resolution. Since the distance to the object is not affected, sensitivity is increased preserving the FoV. Each pinhole generates an image of the object on the detector (see
From elementary geometry, the data recorded by the detector (R) can be shown to be related to the correlation (x) of the source distribution (or object O) with the aperture pattern (A) (see
The aperture pattern A is a generic transmission function ranging from 0 to 1, to indicate, respectively, total opaqueness or transmission to impinging gamma rays. Very often it assumes the simplified form of a square binary array, i.e. whose positions take on two values only, 0's and 1's (see
The importance of the Signal-to-Noise Ratio (SNR) in coded aperture imaging is explained below. The overlap of the different copies of the object in the acquired data makes the relationship between sensitivity and SNR more involved than in systems with no superposition, where the SNR is essentially the square root of the sensitivity. The origin ofthe SNR advantage of coded aperture imaging is best explained in the simple case of a point source. Consider a pinhole camera passing Sij photons. According to Poisson statistics, the variance of this signal is also Sij, so that the standard deviation of the noise is √{square root over (Sij)}, and the SNR is also √{square root over (Sij)}. If a coded aperture made of N pinholes ofthe same size as that ofthe pinhole camera (so that resolution is constant) is used instead, the photons passed are NSij. They are collected at N different places on the detector. These are N independent measurements of the same random variable, so the variance is the sum of the variances, or NSij, and the SNR is √{square root over (NSij)}. Since, depending on applications, N can be 50000 or more, a coded aperture can produce images with the same SNR and resolution of a pinhole camera in a time 50000 times shorter. This enormous advantage ultimately comes from using parts of the detector that, for a point source, would not be used with a single pinhole. Since a larger object would take a larger portion ofthe detector, it is not possible to obtain the same number of separate copies. If copies overlap, statistical independence is not warranted and the SNR argument above does not hold. So, if the object is more complex, the SNR advantage is lower than the theoretical maximum achieved with point sources. A mathematical derivation is needed to quantify the loss (R. Accorsi, "Design of Near-Field Coded Aperture Cameras for High-Resolution Medical and Industrial Gamma-Ray Imaging," Ph.D. thesis, Massachusetts Institute of Technology, Cambridge, Mass., 2001; Busboom et al., "Coded aperture imaging with multiple measurements," Journal ofthe Optical Society of America, A14, 5, 1058-1065, 1997; E. E. Fenimore, supra; and Accorsi, et al., "Optimal coded aperture patterns for improved SNR in nuclear medicine imaging," Nuclear Instruments and Methods in Physics Research A, 474, 3, 273-284, 2001; S. R. Gottesman and S. R. Schneid, "PNP—A new class of coded aperture arrays," IEEE Transactions on Nuclear Science, NS-33, 745-749, 1986). The key concept in these derivations is the concentration parameter. To define it, the FoV is divided in a square grid of as many squares as those forming the coded aperture. These are the reconstruction positions. Sij is the number of counts due to activity present at the reconstruction position (ij) and passing through a single aperture hole. The concentration parameter ψij is defined as:
From its definition, ψij is the fraction of the total activity present at each reconstruction position. It may be different at all points of the image, ranging from 0, for points with no activity, to 1. For example, for a point source, ψij=1 at the source and ψij=0 elsewhere. Notably, that this is the only case in which ψij can be 1. If NT is the total number of reconstruction positions, for a uniform source ψij=1/NT everywhere.
The SNR depends on several other parameters (Accorsi, et al.supra) the most important is ψij. The SNR of the most common pattern family (Uniformly Redundant Arrays, URA) is given by the following equation:
By definition, Sij, the number of photons passing through a pinhole, is proportional to sensitivity. From the equation (10), it follows that, for a pinhole, sensitivity and SNR are equivalent, so higher sensitivity implies higher SNR. For a coded aperture one must first consider whether the increased sensitivity NSij, outweighs superposition losses. In fact, from these two equations, the SNR of a coded aperture equals the SNR of a pinhole multiplied by two factors. The first, always greater than 1, is the number of pinholes in the aperture. The second is the concentration parameter: since it is always less than or equal 1, it represents the SNR loss due to superposition. There is an SNR advantage only at those points for which ψij>I/N. If the object is spread over relatively few reconstruction positions, ψij can be greater than 1/N at all points of the image. At the other extreme, for a uniform activity distribution over the whole FoV, ψij=1/NT, which is always less than 1/N. Therefore, a pinhole can have better SNR at all points of the image. In the great majority of cases bright parts of the image will be better imaged with a coded aperture and dim parts with a pinhole. For example, a calculation for the thyroid study on which many past studies have focused (e.g. J. S. Fleming and B. A. Goddard, supra) shows that coded apertures have only a slight SNR advantage over the pinhole. Cases more favorable to coded apertures, however, are quite common. In fact, if the activity is limited to a fraction f of the FoV, then ψif=1/fNT. From the equations above, it follows that a uniform source confined to a 2×2 cm2 area however distributed on a 9×9 cm2 FoV is imaged with a SNR advantage of about 3.2, which is a factor of 10 in activity or time. If only a narrow line of activity crossing the whole FoV is present (e.g. a capillary tube or a blood vessel), ψif=1/√{square root over (Nt)} and the SNR increases by a factor 4√{square root over (N/2)}.
There have been attempts to improve the system resolution of nuclear imagers by varying a design of a coded aperture such as the size and the number of holes (see R. Accorsi, Design of Near-Field Coded Aperture Cameras for High-Resolution Medical and Industrial Gamma-Ray Imaging, Thesis in Nuclear Engineering, Massachusetts Institute of Technology, May 2001).
U.S. Pat. No. 5,606,165 to Chiou et al. describes a coded aperture imaging system for mapping a radiation exposure in an area.
U.S. Pat. No. 6,205,195 to Lanza describes apparatus and methods for imaging and detection of the elemental composition of an object, wherein gamma-rays having the intensity of at least 1 MeV and emanating from the object are measured by utilizing coded aperture detection systems.
The system resolution of nuclear imagers is usually limited by two factors: the intrinsic resolution of the detector and penetration of the optics. Conventional optical elements of these dimensions cannot obtain sufficient sensitivity. For example, a 10-μm pinhole passes 2.5×10−7 of incident photons at a distance of 5 mm. Accordingly, formation of a clear image requires long acquisition times or use of a level of activity much higher than obtainable in the small volume imaged.
Beekman et al. have recently shown that the use of 125I(27-35 keV) in place of 99mTc (140 keV) photons makes it possible to use 100-μm diameter micro-pinholes and achieve resolution of 184 micron with an Anger camera (see Towards in vivo nuclear microscopy: iodine-125 imaging in mice using micro-pinholes, European Journal of Nuclear Medicine, 29, 7, 933-938, 2002). Sensitivity was about 2.5×10−5 (25 cps/MBq), which is similar to that of 1-mm resolution imagers. This was possible in spite of the dramatic improvement in resolution because the distance to the object was reduced from 33 to 5 mm. The main disadvantage is the reduction in FoV, which is proportional to the reduction in distance from the object. Further, while helpful in the design of the optics, reduced penetration potentially poses a problem of attenuation in the object. It is impractical to further scale down the pinhole when using Anger-camera design. For example, for 10 keV photons and a pinhole aperture angle α=100°, an Au pinhole has an effective diameter of 7.5 μm. At 5 mm from the object, sensitivity would be less than 1.4×10−7 (0.14 cps/MBq). To recover the two orders of magnitude lost in sensitivity, the distance to the object must be reduced by a factor of 10, however the FoV would be reduced to 0.5 mm and the distance to the object would be only 0.5 mm, which may be impractical for many applications. Finally, the intrinsic resolution of conventional Anger cameras worsens with decreasing photon energy. Even assuming an intrinsic resolution in the order of 3 mm, a high magnification of about 300 would be necessary to achieve 10-micron resolution, also setting a limit on the FoV. Attenuation of low-energy photons in any material used to isolate the crystal should also be considered. When low energy isotopes are used to seek high resolution, the performance limit is set by a combination of sensitivity, FoV and distance from the object rather than by penetration. A pinhole cannot provide adequate sensitivity because it cannot be moved closer to the object than in current designs while maintaining a practical FoV and distance from the object. Moreover, a custom-made gamma detector, where crystal thickness would be optimized to avoid degradation of intrinsic resolution is necessary for best performance and may not be justified by efficiency gains. Thus, even though Beekman et al. have achieved a higher system resolution by using a smaller size pinhole and lower energy photons (27-35 keV in place of 99mTc 140 keV), it is impractical to further scale down the pinhole when using Anger-camera design.
Despite the foregoing developments, there is a need in the art for a device and a method of imaging objects on a cellular scale.
All references cited herein are incorporated herein by reference in their entireties.
The use of tracers emitting low-energy photons reduces penetration and typically increases detection efficiency, making high-resolution detectors available. The present invention utilizes 3-10 keV photons to design imaging optics on a scale of a few microns.
The invention describes the design and performance of a high-resolution soft X-ray imager comprising a CCD camera and coded aperture optics to improve sensitivity by several orders of magnitude over conventional optics. Under conditions predictable from theory, the sensitivity improvement translates in full or part to image Signal-to-Noise Ratio (SNR) correct. The system is designed for 280 micron resolution or less and SNR sufficient to produce an image in practical acquisition times (<5 min).
Accordingly, the invention provides a method of imaging a spatial distribution of photon emitters, the method comprising producing an image with a resolution of at most about 180 micrometers using an imaging device comprising a detector and a coded aperture, wherein a photon emitted from the photon emitter has an energy of at most about 35 keV (5.6×10−15 J). In certain embodiments, the energy of the photon is about 1 keV (1.6×10−16 J) to about 10 keV (1.6×10−15 J). In certain embodiments, the photon emitter has energy of at least 3 keV (4.8×10−16 J).
In certain embodiments, the photon emitter is a radioactive isotope of an element. In certain embodiments, the element is at least one of Periodic Table Elements 18 through 80. Preferably, the element is at least one of Periodic Table Elements 18 through 32 and 47 through 80. More preferably, the element is a member selected from the group consisting of Fe, K, Ca, Cr, Mn, Cu, Zn, Co, and I.
In certain embodiments, the resolution of at least about 10 micron is measured over a field of view of at least about 8.2 mm.
In certain embodiments, the imaging device comprises a rotation assembly adapted to rotate the coded aperture by about a 90 degree angle such that at least a portion of near-field artifacts is eliminated from the image.
In certain embodiments, a biological specimen is observed, either statically or dynamically.
Further provided is an imaging device for imaging a distribution of photons having energies of at most about 35 keV (5.6×10−15 J), the imaging device comprising a coded aperture comprising a mask pattern having a plurality of holes, wherein the coded aperture is adapted to provide a resolution of at most about 180 micron, a detector on which a raw image is projected through the coded aperture; and a decoder that receives the raw image from the detector and produces an image having a resolution of at most about 180 micron In certain embodiments, imaging device is adapted to image photons emitted from a radioactive isotope of an element. In certain embodiments, the system resolution is at most 20 micron. In certain embodiments, the resolution of at most 20 micron is measured over a field of view of at least about 5 mm.
In certain embodiments, the system resolution is from 20 micron to about I micron.
In certain embodiments of the device, at least a part of the coded aperture is manufactured from at least one of tungsten, molybdenum, gold, copper, and manganese, a combination thereof and alloys thereof. In certain embodiments, at least a part of the coded aperture further comprises a supporting substrate.
In certain embodiments of the device, the coded aperture comprises a 604×604 No-Two-Holes-Touching (NTHT) MURA pattern with about 10 micron holes and a 1/32 open fraction. In certain embodiments of the device, the coded aperture comprises gold and an alloy of NiCo.
In certain embodiments, the device further comprises a rotating assembly associated with the coded aperture, wherein the rotation assembly is adapted to rotate the coded aperture by about a 90 degree angle such that at least a portion of near-field artifacts is eliminated from the image. In certain embodiments of the device, the rotating assembly is associated with a linear stage adapted to move in X, Y and Z directions.
In certain embodiments, the device further comprises an object holder adapted to hold a photon emitter, wherein the object holder is capable of movement in the X and Z direction to coordinate a focal plane with a detector plane to provide a first distance from the detector to the aperture of about 30 to about 40 mm and a second distance from the detector to the object of about 40 to about 60 mm.
In certain embodiments of the device, the object holder is further adapted to hold a biological specimen. In certain embodiments of the device, the biological specimen is a cell, tissue, organism or multi-cellular organism.
The invention will be described in conjunction with the following drawings in which like reference numerals designate like elements and wherein:
The invention was driven by the desire to develop a device capable of imaging objects on a scale of 280 microns or less. In the present invention, the synergy is achieved by the combination of low-energy photons (to obtain reduced penetration and high detection efficiency), a CCD detector (to obtain high-resolution), and coded aperture optics (to obtain high sensitivity and SNR). The low penetration of 3-10 keV photons in heavy materials opens the opportunity of designing high-resolution optics. The small solid angles involved cause low sensitivity but counts can be recovered with a desired coded aperture. A tool capable of imaging directly not large molecules, but single atoms, in a relatively short time, is appealing because of its potential for translating molecular imaging techniques to the space scale of a human somatic cell, thus making a powerful modality available to investigators in basic life science research.
The present invention can be used to study objects on a cellular scale to investigate, for example, the role of isolated ions as well as small and large molecules without altering their physicochemical properties. For its unprecedented resolution, the device has beyond state-of-the-art performance and opens an entirely new realm of potential applications. While it is difficult to predict the specific applications of the invention, it is reasonable to expect in vitro and in vivo applications to fundamental cell biology questions such as diffusion mechanisms and cell trafficking. The device of the invention, a soft-X-ray microscope, will make it possible to follow the evolution over time of the spatial distribution of biologically relevant isotopes, preferably elements from P to Ge, and more preferably K, Ca, Cr, Mn, Fe, Cu, Zn and I, with a resolution on the spatial scale of human cells. Low-energy photons do not penetrate the relatively heavy materials ofthe optics and the detector, but are also absorbed in the sample. A typical value is 50% attenuation of 5.89 keV (55 Fe) photons in 266 μm H2O.
Advantageously, this invention utilizes low penetration in photon detection. Low energy photons can be stopped with good efficiency within thin materials. This helps high resolution imaging for two reasons. First, because pinholes have a smaller effective diameter; and, second, because low energy photons deposit their energy in a very localized fashion and can be detected with excellent intrinsic resolution. Photons in the 3-10 keV range can be stopped in less than 100 μm of silicon with efficiencies from 30 to 75%. In commercial X-ray CCD cameras, typical pixels have a width of a few tens of microns or less and the intrinsic resolution is essentially equal to the pixel size. For this reason, a large magnification is not needed to achieve resolutions ofthe order of the pixel size, and the FoV of the instrument is essentially the active area of the detector, which is about 2-3 centimeters. A custom-made Anger camera typically has a 10-cm crystal. Even assuming an intrinsic resolution of 1 mm, to achieve 10-μm resolution magnification would need to be about 100, which would reduce the FoV to 1 mm. Other favorable characteristics of CCD cameras include negligible readout noise with little contribution from dark current when the camera is cooled with liquid nitrogen, a standard and commercially available option. CCD technology also offers the advantages of an available, practical and relatively inexpensive technology.
The invention provides a method of imaging a spatial distribution of photon emitters, the method includes producing an image with a resolution of at most about 180 microns using an imaging device comprising a detector and a coded aperture, wherein a photon emitted from the photon emitter has an energy of at most about 35 keV (5.6×10−15 J). In certain embodiments, the energy of the photon is about 1 keV (1.6×10−16 J) to about 10 keV (1.6×10−5 J). In certain embodiments, the photon emitter has energy of at least 3 keV (4.8×10−16 J). Further provided is an imaging device for imaging a distribution of photons having energies of at most about 35 keV (5.6×10−15 J), the imaging device comprising a coded aperture comprising a mask pattern having a plurality of holes, wherein the coded aperture is adapted to provide a resolution of at most about 180 micron, a detector on which a raw image is projected through the coded aperture; and a decoder that receives the raw image from the detector and produces an image having a resolution of at most about 180 micron Further, imaging device comprises an object positioning system and a mask rotation system.
The invention will now be described in more detail below.
Detector Design
In certain embodiments, the detector is selected from the group consisting of pixelated (Nal, YAP:Ce, CsI) crystals coupled to a position sensitive photomultiplier tube (PSPMT), pixelated YAP:Ce on PSPMT, pixelated CsI on PSPMT, continuous Nal crystal directly coupled to PSPMT, Cs(I) coupled to a silicon drift detectors (SDD), CdZnTe arrays, 0.6mm for 57Co, and a charge-coupled device chip. In certain embodiments, the detector is the charge-coupled device (CCD) chip. In the preferred embodiment, the detector is a Charged Coupled Device (CCD) chip, which is selected because of its high efficiency and resolution for photons in the range of interest, i.e. 3-10 keV. The CCD cameras can be of a deep-deletion or a non-deep-depletion type and also further distinguished as front- or back-illuminated. Depending on the specific type of detector, and especially on whether the detector is of deep-deletion type and if it is front- or back-illuminated, desired efficiency based on % of photons detected can be selected for the photons of interest. Non-deep-depleted devices have an efficiency lower by a factor of 2 or 3 as compared to the deep-depleted devices, as the depleted region is not as extended as in deep-depleted devices. These detectors may still be a practical solution because, due to their lower cost, several units can be utilized to recoup the sensitivity loss.
In the detector, different chips offer different pixel sizes in a range, for example, from about 10 to about 25 μm. Resolution is very close to these values, even though part of the charge may be shared by first neighbors, thus spreading the event over different pixels ("split" events). In certain embodiments of the invention, this decrease in resolution is accepted; in other embodiments, "split" events are rejected by using spectroscopy techniques since the expected count rate is very low and that chips can be read out very quickly.
In the preferred embodiment, the CCD camera sensible to X-rays is the commercially available PI-LCX:1300/LN (Princeton Instruments, Trenton, N.J.) which is a silicon deep-depletion, front-illuminated 1300×1340 array of 20×20 μm2 pixels. Efficiency is appreciable in the 2-20 keV range, above 30% from 3 to 10 keV, and peaks at 75% between 5 and 6 keV. The Be window used to maintain vacuum with minimal attenuation for detector cooling purposes has the added benefit of blocking <2 keV photons. The CCD is a 1340×1300 array of 20×20 μm pixels.
In high-resolution applications in which small activity distributions are studied, very low count rates are expected at the detector. An overestimate of the expected activity in the sample is 100 μCi (3.7 MBq). Assuming a distance of 5 cm from the detector, the count rate expected is 1.177 104 cps/cm2. Assuming 10×10 μm2=10−6 cm2 pixels the expected count rate in each pixel is 1.177 10−2 s−1, which is about 0.7 counts per minute. A more typical count rate is at least a factor of 10 less than this, i.e. about 0.35 counts per pixel every 5 minutes, which we regard as an upper limit for an acceptable exposure time.
CCD Spectroscopy
Assuming 70% detection efficiency, this means that there is a
Chip readout times can vary depending on the desired application, however they would have to be balanced to account for noise introduced at longer exposure times. If long exposure times are used, it will eventually become very unlikely that pixels will see single events. For example, after 1 hour, 75% of pixels will have 2 or more events. If spectroscopic information is necessary, for example to reject scattered events, the detector needs to be read out and the acquisition restarted. The drawback of this technique is that it imposes some deadtime. Typical readout frequencies are 50 kHz and 1 MHz. The first value results in a long read time but is affected by lower readout noise. For a 1340×1300 pixel detector, 1.742 million pixels need to be read, which takes about 35 s at 50 kHz vs. 1.7 s at 1 MHz. At 50 kHz the read noise is 13 e− or less, whereas at 1 MHz it is 30 e− or less. In the preferred embodiment, the signal is at least 3 keV/3.62 eV (energy per e−-hole pair in Si)=829 e−, resulting in a better than 4% electronic noise.
Spectroscopic information possible is expected to be helpful in the discrimination of scatter and spurious events such as cosmic rays. The latter are expected for exposure times as long as 5 min and may influence significantly the reconstruction ofthe multiplexed data because they typically deposit a large energy density.
Under these conditions, the single most important characteristic is indeed not read noise, but detector dark current. Assuming that X-rays form the most commonly available isotope in this energy range, 55Fe (5.89 keV, t1/2=2.73 y), every detected event will produce 5890 eV/3.62 eV≈1600 pairs. This is the signal, compared to which the number of electrons that accumulate in each well. Dark current accumulates e−-hole pairs at a rate depending on factors such as material and pixel volume; the order of magnitude is 100 e−/s in each pixel at 20° C. Over a 5 min acquisition time, 3 104 e− are collected, which is a level much larger than the signal. However, these pairs are generated thermally and the production rate can be decreased dramatically by reducing temperature. Below −50° C. the temperature dependence is the same for Advanced Inverted and Non-Inverted Mode Operation chips. It is:
All commercially available systems offer solutions for cooling. The detector and cooling systems are encased in a vacuum to reduce heat exchange with the environment. A 10-μm beryllium window is used to separate the vacuum from the environment while providing minimal attenuation for incoming photons. The beryllium window is also helpful in modulating the efficiency curve by passing only photons with relatively high energy. Other materials can be used in place of beryllium such as, for example, MYLAR.
Further, each pixel can contain a limited number of e− before it overflows spilling charge to neighbors in its column (blooming). Typical capacities depend on operation mode and may be as low as 3 105 e−. In our case this is equivalent to about 190 events. Since only a few are expected, well depth is not likely to be a limitation and blooming a problem.
Consequently, in normal operation, fast readout (about 1 MHz) is likely to find application if spectroscopic data are needed, but it will not be necessary to reduce dark current buildup or avoid blooming. During the setup and alignment of the system, however, it will be convenient to be able to produce quickly a series of images.
Since dark current is extremely low, especially at 163 K, accurate temperature control is not necessary. However, keeping dark current at a known and repeatable low level will stabilize the correction for background events.
All CCD chips may have fabrication defects and are classified by grade. The lower the grade, the fewer defects are present, but even a grade 0 chip, in spite of its cost, is not free of defects. These include pixels that spontaneously appear bright in the image, pixels that appear dark and columns that also appear dark starting from a certain point and extending to the edge of the detector. For the CCD 36-40 (Princeton Instruments, Trenton, N.J.), a grade 0 chip has up to 65 white spot defects, 50 dark spots and no dark columns. For grade one, these numbers are, respectively, 105, 100 and 3. The implications of these defects in terms of image quality can be evaluated only in connection with the design of the coded aperture.
A Coded Aperture or a Mask Design
Due to the limitations of current fabrication technologies, the size of the coded aperture is related to its thickness. If small features are needed, the thickness ofthe mask is limited. The minimum thickness is determined by the transparency of the mask material to X-rays, which depends on the energy of the photons as well as on the material of the aperture. Different materials, two levels of attenuation (97% and 99%) and two energies (5.89 and 10 keV) were analyzed, and results are presented in Table 1 below.
The materials chosen were tungsten and molybdenum (the most common options for photo-etching fabrication), gold (selected for its high density and attenuation coefficient), an alloy of NiCo and copper (which are used as substrate in electroforming). An excellent option to stop Fe X-rays (5.89 keV, the most commonly available isotope in this energy range) is to use the immediately preceding element in the table ofthe elements, which is Mn (notably, Mn is not available at the present time for the preferred fabrication technique (i.e., electroforming)). The preferred material is then gold, as it requires the thinnest thickness to stop a given fraction of X-rays. About 5 μm of material is sufficient. Also, this material will have to be supported by a substrate for mechanical stability. A non-limiting example of the substrate material is NiCo, which can provide stable substrates as thin as, for example, 5 μm, for a total thickness of about 10 μm.
The aspect ratio achieved by most techniques is usually about 1:1, so that it is possible to fabricate holes with a side of approximately 10 μm. This is more readily achieved by electroforming. Other techniques include but not limited to electrical discharge machining (EDM), photoetching, and laser drilling. Electroforming has a limitation on the minimum center-to-center spacing between holes, which can be estimated as a distance of 2×thickness+feature diameter +10 μm. In this case, the sum is 40 μm. This minimum distance (i.e., 40 μm) precludes the use of No-Two-Holes-Touching (NTHT) MURAs with an open fraction of ⅛ because the minimum center-to-center spacing between holes is twice the size of the holes. The NTHT MURA masks are described by Accorsi et al., supra.
The coefficient of attenuation at 5.89 keV for Au is 438 cm2/g (see Table 1). Only 5.4 μm of material are needed to obtain 99% attenuation, which can be plated on a substrate of 5 μm NiCo for mechanical stability by electroforming (Metrigraphics, Wilmington, Mass.). Since holes have a 1:1 aspect, the minimum hole size is 10 μm and the minimum hole-to-hole distance to 40 μm. Since the projection of a hole on the detector needs to be sampled with a minimum of 2 pixels, a square coded aperture can have at most 650 positions and the minimum magnification m, defined for coded apertures as the ratio of the size of the projection of a hole on the detector and its actual size pm, is 4. These parameters determine, respectively, the pattern size and most other dimensions of the optics.
The pattern choice is an important consideration in the design of the mask. The NTHT MURA family can be used to generate an array with the correct minimum spacing at the cost of accepting an open fraction of 1/32. An open fraction 4 times lower has a clear impact on sensitivity, which is reduced by a similar factor. The impact in terms of SNR depends on the concentration parameter ψ.
In the preferred embodiment, the NTHT MURA pattern with 10 μm holes and a minimum distance of 40 μm was obtained by setting the parameter e to 4 (see Accorsi, et al., "Optimal coded aperture patterns for improved SNR in nuclear medicine imaging," Nuclear Instruments and Methods in Physics Research A, 474, 3, 273-284, 2001), which sets ρ= 1/32. The largest anti-symmetric pattern with fewer than 650 positions was 604×604. With ρ=⅛ (the usual choice for e), the pattern would have been 622×622. 604×604 and patterns of the same or different array family leading to similar resolution and field of view when used in similar geometry.
The SNR of coded apertures depends on the distribution of activity in the object, which is described with the concentration parameter ψ. If Si is the number of counts due to source photons reconstructed at the ith pixel of the image and passing through a single aperture hole, then ψi=Si/ΣiSi. The SNR of NTHT M URA patterns as a function of ψ and ρ has been defined in Accorsi et al., supra.
The projection of a mask pixel onto the detector needs to be sampled by at least two pixels if the maximum reconstructed intensity of a point source should not, as desirable, vary with its position. Since pixels are 20-μm wide magnification (in a coded aperture definition) needs to be at least 4.
The largest square imaging area ofthe LCX 1300 is 1300×1300 pixels, so that the largest pattern is 650×650. Since a spacing of 4 mask positions is needed between first neighbors, the MURA at the basis of the NTHT pattern is at most 162×162. The largest anti-symmetric pattern available is 151×151, resulting in an NTHT pattern 604×604. For this pattern the largest sampling parameter α is 1300/604=2.15, resulting in a maximum magnification of:
The dimension of the resolution element allows the calculation of the concentration parameter. For a source uniform over the cross section of a 250 μm-diameter bead (4908 μm2), ψ=3.4 10−3. This value is important because it shows that for commercially available point sources (IPL labs, Valencia, Calif.), ψ is such that the difference in terms of SNR for a ⅛ or a 1/32 open pattern is minimal.
From the geometric parameters calculated above it is now possible to estimate the sensitivity from a purely geometric calculation of solid angle. This is easy in the assumption of ideal mask, i.e. perfectly opaque and infinitely thin. Consequently for an object-to-pinhole (or coded aperture, which is the same) distance of about 1 cm, sensitivity is about 8 10−4 for the coded aperture and 8 10−8 for the pinhole. Accordingly, the equivalent number of pinholes is about 104.
In a preferred embodiment, to obtain 1% attenuation, 5.4 μm Au are necessary. This amount can be plated on a 5-μm NiCo support for mechanical stability. Usually, coded apertures are fabricated with an open fraction ρ=˝ or ρ=⅛, but this is incompatible with the limit set by fabrication considerations that the minimum size of the holes be 10 μm with 40 μm spacing. For this reason, a pattern with ρ= 1/32 was adopted (604×604 NTHT MURA). Despite a significant reduction in sensitivity with respect to more open arrays, the reduction in SNR is minimal for ψ<10-2. For reference, for a 250-μm disk W-3 10−3.
Sensitivity depends on the distance from the object.
Correction of Near-Field and Misalignment Artifacts
In one embodiment of the invention, a mask rotation system is used to correct, reduce or eliminate the near-filed and misalignment artifacts. Near field artifacts arise when the coded aperture arrays developed for far-field applications are used in the near-field (see R. Accorsi and R. C. Lanza, "Near-field artifact reduction in coded aperture imaging," Applied Optics, 40, 26, 4697-4705, 2001).
The artifacts appear when gamma rays originating from the same point in the FoV reach the detector with different incidence angle, a situation forced by the need to maintain a short distance from the object to maximize sensitivity. Under these conditions, the linearity of the equation (5) is violated and the procedure to undo the overlap does not produce an exact copy of the object. One remedy is based on the following: if the exposure time is divided in two halves and two images are taken, one with a mask and one with a mask with open and closed positions exchanged (the anti-mask) and the result added, artifacts, which affect both images, cancel in the sum. From a practical point of view, it is very advantageous to choose a mask with an axis or a center of odd symmetry, such as the mask of
As described in a published application US 20020075990A1 by Lanza et al., reducing and/or eliminating artifacts in near field imaging applications can be achieved by combining images obtained from passing a signal through (i) two masks having decoding arrays which are negatives of each other (a mask and a negative mask), wherein the masks are consecutively placed or (ii) one mask which is then rotated about its center by a certain angle (e.g., 90°). Further, a single detector detects signals passing through the first mask and then, the second mask wherein the second mask can be a separate mask from the first mask or it can be the same mask, which is rotated by 90°.
In certain embodiments of the device ofthe invention, near-field artifacts are corrected by using an anti-symmetric pattern so that an anti-mask is obtained by a 90° rotation of the mask (as described by Lanza et al., supra and R. Accorsi, supra). Acquiring a mask and an anti-mask image is helpful in reducing near-field artifacts and compensating detector non-uniformities.
In certain embodiments, to avoid misalignment artifacts without relying on image manipulation, the position of the coded aperture would have to be adjusted to be within 15 μm (or other desired resolution of at most 280 micron (μm)) and 6 arc min. As shown in
In certain embodiments, eliminating near-field artifacts is done by utilizing two detectors and therefore increasing efficiency and eliminating the need to rotate the mask. Coded apertures could be mounted directly on the object holder because their rotation with respect to the object is no longer necessary. Correction of artifacts utilizing the plurality of detectors and the plurality of coded apertures at about a 90 degree angle relative to each other is described in detail by the inventor in a co-pending application entitled CODED APERTURE IMAGER WITH NEAR FIELD ARTIFACT CORRECTION FOR DYNAMIC STUDIES filed on even day with the present application.
Detector Mount and Object Positioning Equipment
The best way to demonstrate 10-μm resolution is to use two point sources at different distances, for example ever micrometer from 5 to 15 μm, and then verify that the image of the two point sources is distinct only for a spacing larger than 10 μm. Real point sources, however, have finite size and can be considered point-like only if their size is much smaller than the resolution of the instrument. In this case, this would be about 1 μm or less. The smallest sources obtainable, however, are, to our knowledge, in the range of at least a few tens of micrometers (see English et al., "Sub-Millimeter Technetium-99m Calibration Sources," Molecular Imaging and Biology, vol. 4, no. 5, pp. 380-384, 2002). Thus, it is likely that resolution will be measured with some other method, e.g. as those based on following the known motion ofthe centroid of a given activity distribution. For the reasons mentioned above, such motion would need to be controlled with a precision of about 1 μm. Also, it is assumed that the rows and columns in the aperture will be parallel to those of the detector pixels. The precision to which these relative rotation angles should be measured can be obtained from the number of detector pixels. If the projection of each mask hole falls on two detector pixels, it is reasonable to expect that significant disruption of the reconstructed image will start to appear when the mask is rotated by an angle such that displacement at the edge ofthe detector is one pixel. Simulations confirm this estimate. Since the largest square field of view of the detector has 1300 pixels on its side, this angle is given by at an (1/650) <0.1=6 arc min. The rotation stage will need to position the coded aperture with this order of absolute precision or better.
The preferred embodiment of the device of the invention is shown in
The second column is used to position and move the object. Two linear stages 40 and 42 (DS40-X and DS40-Z) are similar to those in the other column. X direction indicates movement in side to side direction in the plane of the
Calibration Sources and Design
Ion exchange 55Fe microbeads with a diameter of 250 μm and activity between 10 and 100 μCi are commercially available (IPL Labs, Valencia, Calif.) for calibration and performance evaluation. Custom sources with 40-100 μm diameter can be prepared conveniently in a nuclear medicine laboratory using guidance from English et al., supra.
As predicted by theory, simulation confirms that only the coded aperture can produce an image of this source. The simulation in which a single cell is injected to study how the tracer diffuses over time was conducted to study the activity distribution. In the simulation, a pinhole and a coded aperture (604×604 NTHT MURA pattern with 10 μm holes and 1/32 open fraction) were utilized with a 250-μm 55Fe disk; activity was 370 kBq and the acquisition time was 300 s. Clearly, only the coded aperture produced an image in a cellular scale distinguishable from noise or artifacts.
The performance of the device described above was simulated and the expected image was reconstructed after a 10-min exposure of a 10 μCi source having a diameter of 250 μm as shown in
As in all linear imaging systems, the single most informative performance check is the acquisition ofthe Point Spread Function (PSF). In theory, this operation requires the availability of a dimensionless point source, but in practice a source with dimensions much smaller than the resolution of the instruments are sufficient for a significant test, i.e., a source with dimensions in the order of 1 μm.
The preferred isotope is 55Fe, because it decays by electron capture to a stable isotope, so that it does not emit any charged particles. Its only emissions are X-rays from the electronic shell of 55Mn and are in the range 5.888 to 6.490 keV. The half life of 55Fe is 2.73 years. Assuming a density of 7.88 g/cm3, a 1-μm-diameter sphere of pure 55Fe has a weight of 4.12 pg, corresponding to 4.52 1010 atoms, for an activity of about 365 Bq (10 nCi). Thus, even if it were possible to fabricate such a sphere, its activity would be impractically low.
Activity is inversely proportional to half-life, and other isotopes can be used. Non-limiting examples of other isotopes include 51Cr, which also decays by electron capture to a stable isotope (half-life 271 days), but emits a 320 keV (yield 10%) γ ray along with X-rays (4.945-5.427 keV, yield 23%); and 58Co (half-life 71 days), which may emit a positron (14% yield) along with a 810 keV photon and iron X-rays.
At these energies attenuation and stopping coefficients are such that shielding aiming at stopping relatively high-energy charged particles will also stop relatively low-energy photons, i.e. the signal. Charged particles can disturb the image. Therefore, an isotope emitting no charged particles such as 55Fe is preferred. However to increase the count rate, other isotopes can be used also, wherein charged particles can be stopped with the help of a magnetic field and discriminated from photons events in the detector by energy discrimination.
While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.
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Birch Stone BirdbathLO-2297 In Stock
- Proudly constructed in the USA from premium cast stone concrete.
- The Birch Stone Birdbath is available in your choice of classic and distinct Henri Studio finishes, each applied by hand.
- Designed to last a lifetime
- Each piece weathers naturally over time.
- 2-piece assembly.
- The Birch Stone Birdbath is 18" wide and 28" in height. Total weight is 68 pounds.
- Notes:Shown in Hi-Tone (HT) finish.
Bird ornament no longer included/available.
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SpecificationsMade from Premium Cast Stone
Dimensions: 18" W x 28" H
Weight: 68 lbs.
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There are 22 meeting rooms available for conferences, banquets, and meetings for all Registered Student Organizations, University departments, professional organizations and the community. The West Suite can be divided into three individual rooms. East Ballroom can be divided into two large rooms. RSOs must also adhere to the RSO Food/Catering Policies.
RSOs may use meeting rooms at the Bernhard Center to conduct regular weekly business meetings at no charge.
A $100 deposit is required when reservations involve ballroom use, sales (items for sale may not duplicate or compete with items sold by merchants in the Bernhard Center), concerts, fundraising events and catered events. The balance of the rental fees will be due no later than one week after the event has taken place. The reservation deposit will be subject to forfeiture if a reservation is not cancelled 90 calendar days prior to the event.
The set-up of meetings rooms for RSOs at no charge will be used "as is" - no special set-ups.
A Bernhard Center Usage Agreement form for all RSOs must be completed prior to confirmation of any facility use that requires rental or fees charged.
Rental of rooms covers the period of time stated on the Bernhard Center Usage Agreement Form available at the Bernhard Center office.
All charges are the responsibility of the RSO: in the event a payment is not made, the individual who made the reservation will be held financially responsible.
A temporary hold may be requested for a given space with the following restrictions:
· Temporary hold will not be converted to a firm reservation until a Bernhard Center Usage Agreement (at Bernhard Center office) is signed with appropriate deposit made.
· Temporary hold must be converted to a firm reservation within 30 calendar days or the hold will be cancelled
RSO must notify Bernhard Center main office for reservations, cancellations or changes for room use.
Due to high demand by RSOs, meeting rooms may be occupied for no more than three hours. The set-up for the second meeting reservation will remain the same as the previous group.
New WMU student organizations that have registered with the Student Activities and Leadership Programs office will have the privilege to use Bernhard Center meeting rooms and facilities during their one month probationary period.
All RSOs using a fund and cost center require pre-authorization of funding source to use Bernhard Center facilities where a charge is applicable.
Use of rooms and facilities in the Bernhard Center is reserved for the groups registering for these rooms and guests only.
Organizations will be held responsible for the condition of rooms used. This includes the clean up of food brought into meeting rooms. Any damage will result in a direct charge to the organization or individual making the reservation.
No tape, tacks, nails, pins, staples, etc. may be used on any papered, paneled or painted surfaces or on any walls, mirrors, windows, curtains, or doors. Freshly cut flowers, properly maintained live trees, plants and shrubs may be used for decorative purposes. Decorations cannot be placed in an area that blocks an exit due to Fire Safety Regulations.
The Bernhard Center cannot store any decorative items or equipment.
Groups sponsoring political candidates for appearances at the Bernhard Center must be pre-registered with the SALP office prior to the use of the Bernhard Center facility.
See Dance and Ball Guidelines (available at Bernhard Center Main Office) for any dances.
Bernhard Center policies are outlined in the RSO Handbook.
For questions and information concerning Bernhard Center policies, please contact the Resource and Graphic Design Center.


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Africa's phenomenal growth has made it an economic powerhouse, creating wide ranging opportunities for Africa-UK trade and investment. Using the strength of the Deloitte's global network, we are able to guide and advise UK and African companies doing business between the two markets.
To see what CFOs across 14 European countries think please go to our European CFO Survey page.
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The trashy, disgusting ranch eating part.
8/7-8/9: Outside Lands Music Festival
8/8: Holly Herndon @ The Chapel
8/11: Screaming Females @ The Rickshaw Stop
8/14: John Roberts, Laurel Halo @ f8
8/20: The Sandwitches @ The Chapel
8/22-23: FYF Fest
8/29: King Gizzard and the Lizard Wizard @ The Rickshaw Stop
9/18: Octave One @ Mighty
9/20: Max Graef, Huxley, Glenn Astro @ The Midway
9/23-27: Decibel Festival
9/29: Titus Andronicus
I wish Wham! Would reunited on the Polo Fields.....no regrets
Swans @ Terminal West 03/28/15
Drive like Jehu @ The Glass House 04/08/15
Electric Wizard @ Slims 04/17/15
Acid Mother Temple @ BOTM 04/18/15
Faith No More @ the Warfield 04/20/15
John Zorn @ UCLA 05/02/15
Will Bulter @ Slims 05/26/15
Neutral Milk Hotel @ Pappy & Harriets 05/30/15
Mariah Carey @ Caesars palace 06/11/14
I am not going to Coachella this year. I am hoping Guedita will wave at the camera in case I can catch some of the webcast.
"why are you so annoying" TheKlein25
An employee caught me laughing so hard tears were running down my face. She wanted to know what was going on. All I could do is choke and point at this on my computer screen
"why are you so annoying" TheKlein25
Come on people, muthafucken GRUMPY CAT, where is the love
"why are you so annoying" TheKlein25
New Order has grumpycat avatar on the coachella.com.
My ass hurts, I hope I am not getting colon cancer.
"why are you so annoying" TheKlein25
skipped a morning of applying hemorrhoid cream. Just wasn't in the mood to stick that anal applicator up my butt.
Bought a bunch of weed products at a new spot 'One Love' in Westminster. Love those stores. 5gram Private Reserve OG, Medicaps, ganja rub, bhang bars.
Ahhhhhhhhh I love talking to old friends. 90% of them are fucking losers that make me feel so much better about my shitty decisions. Not that I make bad decisions, I'm just way too hard on myself.
I couldn't find my keys because they were underneath my viking hat.
That's why I keep a specific spot for my Nordic accessories
Metz - 8/15 - Red 7
Belle & Sebastian - 8/28 - ACL Live
Godspeed You! Black Emperor - 9/14 - The Mohawk
Chelsea Wolfe - 9/19 - The Mohawk
Titus Andronicus - 9/20 - Red 7
Thee Oh Sees - 9/23 - Hotel Vegas
I'll try to make it short. This was a few years back.
Coolest grandfather dies.
Following winter, shitty widowed grandmother sold some family heirlooms including items left to me in grandfather's will. She was financially sound regardless.
Following spring, finished paying my own tuition via scholarships and money saved.
Asked by grandmother if I'd afford final term in undergrad.
Said "No."
Received funds.
Absconded to a Puerto Rico resort for spring break.
Never a regret.
I have a different Grumpy Cat shirt for each day of Coachella.
"why are you so annoying" TheKlein25
When I was 5 I struck out on the T in T ball. Yes it is humanly possible to do that.


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August 4, 2015
BRYAN A narcotics search warrant lands a Houston woman and a Bryan man in jail for manufacturing and delivery of a controlled substance.
37-year-old Dreamer Shante Brown and 33-year-old Patrick Jazzaree Gilmore were arrested Thursday during a raid on house in the 2800 block of Cypress Bend.
According to the police report, investigators found Brown and Gilmore inside the home they raided. After a search of the house, officers found 23 rocks of crack cocaine and five pills of MDMA.
There were also two cell phones that had no texts messages, but numbers saved in the address book consistent with what investigators believed were drug users. There was also a video on one of the phones that recorded a conversation between Brown and Gilmore where they talked about the use of illegal drugs.
Brown is in jail under $45,000 bond. Gilmore is being held under $31,000 bond.
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Two children were removed from a Winona Lake home Tuesday night after police say they found an active meth lab in the residence.
Two children were taken into Child Protective Services' custody Tuesday night after police found an active meth lab in a Winona Lake home.
Narcotics officers from the Winona Lake and Warsaw police departments were called to a lot in the Fair Lane Trailer Park at 1202 Wooster Road around 8 p.m. Tuesday, Aug. 19, on a tip that someone manufacturing methamphetamine in the home.
The officers found drug paraphernalia and a one pot meth lab in the trailer.
The renters of the property, Joseph Werand and Christy Bodkin, were in the home at the time. Two others, Todd Rany of Rochester and James Page of Winona Lake, were also at the home.
The officers interviewed the subjects and determined all four had used meth earlier in the day at the home.
Two children, ages 9 and 10, were also at the home. They were taken by Child Protective Services for a medical checkup.
Bodkin and Werand were arrested on a preliminary charge of maintaining a common nuisance. Bodkin was also arrested on a charge of neglect of a dependent.
Raney was arrested on preliminary charges of possession of methamphetamine and aiding in the manufacturing of methamphetamine.
Page was arrested on a preliminary charge of visiting a common nuisance.
Officers from the Winona Lake and Warsaw police departments were assisted by the Indiana State Police Clandestine Lab team to clean up the lab.


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Bishop England picked up three impressive victories last week and remains No. 1 in Class AA in the latest state baseball coaches poll.
The Bishops topped Hanahan 8-0, Wando 11-2 and Goose Creek 13-2 to up their record to 5-1.
The Bishops had plenty of hitting as Tradd Lowman and Cameron Garrett both hit homers in the wins over Hanahan and Wando.
The Bishops host Summerville tonight.
Wando and James Island were ranked in the top 10 in Class AAAA and AAA, respectively, but fell out of the polls this week.
Class AAAA
1. Lexington
2. Conway
3. Sumter
4. Mauldin
5. South Aiken
6. Northwestern
7. West Florence
8. Blythewood
9. Nations Ford
10. Easley
Class AAA
1. AC Flora
2. Greenville
3. Belton-Honea Path
4. Chapin
5. Wren
6. St. James
7. Emerald
8. Eastside
9. Airport
10. Gilbert
Class AA
1. Bishop England
T2. Dillon
T2. Chesterfield
4. Mid-Carolina
5. Andrew Jackson
6. Chesnee
7. Andrews
8. Pendleton
9. Ninety-Six
10. Abbeville
1A Poll was not available at the time of posting
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31 Mar 20103 Comments
Do the MDGs influence national development policies?
Expect a lot of soul searching around the Millennium Development Goals (MDGs) this year, in the run up to the UN high level event in September (see previous posts here and here). A recent issue of the IDS bulletin covered 'The MDGs and Beyond'. The piece that caught my eye was an... Read More