two hundred and fourteen patients received a total of 234 hsct at our institution between may 2007 and december 2013 . during the study period , upper and lower gi endoscopic examination and biopsy were performed for histological assessment when it was necessary 9 , 10 . us was performed using a pvt674 bt ( center frequency , 6  mhz ) and 704at / bt ( center frequency , 7.5  mhz ) equipped with aplio xv / xg/500 ( toshiba medical systems corp . , otawara , japan ) . seven segments of the gi tract were sequentially and individually assessed , including the stomach , duodenum , jejunum , ileum , rightsided colon , leftsided colon , and rectum . in this study , five registered medical sonographers in gastroenterology who had more than fiveyr experience performed us examinations . the thickest and widest parts in each segment were measured to determine the thickness and dilatation , respectively . abnormal thickening of the gi tract wall was defined as a thickness > 5  mm in the stomach and rectum , and > 3.5  mm in the small intestine and colon 11 , 12 , 13 . the thickness of internal low echoic layer reflecting inflammation of the mucosa , muscularis mucosa , and submucosa was measured as a representative of inflamed layer in the gi wall . dilatation of the intestine was defined as a diameter > 18  mm when filled with fluid 14 . measurements of the gastrointestinal ( gi ) tract wall . the thin echoic line in the middle of the internal echo poor layer reflects an interface layer between mucosa of the ventral and dorsal part of the gi tract . the thickest part is measured for the thickening of the gi tract wall ( a ) , the largest part for the diameter of the gi tract ( b ) , and the thickest part for the thickening of the internal low echoic layer ( c ) . color doppler imaging was concomitantly performed , with color gain adjusted until disappearance of noise for maximization of the sensitivity . color doppler frequency was set from 3.3 to 7.2  mhz , pulse repetition frequency from 4.7 to 10.1  cm / s , which was adjusted according to the type of probes and the depth of the lesion . increased doppler signaling was defined as spotty to linear color doppler signaling in mucosa and submucosa . it took about 520  min to assess entire gi tract by us , depending on the findings . us detects five layers of the normal gi tract wall 10 , 15 , 16 , 17 , 18 ( fig .  2 ) . we classified gigvhd into four grades according to the us findings of the five layers . the first layer corresponds to the border echo and a part of mucosa , the second layer is the rest of mucosa , the third layer is muscularis mucosa , submucosa , and a part of muscularis propria , the fourth layer is the rest of muscularis propria , and the fifth layer is serosa and border echo . a truepositive ( tp ) us corresponded to positive  us findings in patients with gigvhd . a truenegative ( tn ) us was defined by the absence of gi tract findings in patients without gigvhd . a falsenegative ( fn ) us corresponded to the absence of us abnormalities in patients with gigvhd . a falsepositive ( fp ) us corresponded to the findings of more than us grade 1 in patients without gigvhd . us findings and reference diagnosis methods of acute gigvhd were compared using sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) . the correlation between the stage of gigvhd and each us finding was evaluated by spearman 's rank correlation coefficient analysis . statistical analyses were performed using standard statistical software ( ibm spss statistics version 20.0 for mac os , chicago , il , usa ) . two hundred and fourteen patients received a total of 234 hsct at our institution between may 2007 and december 2013 . during the study period , upper and lower gi endoscopic examination and biopsy were performed for histological assessment when it was necessary 9 , 10 . us was performed using a pvt674 bt ( center frequency , 6  mhz ) and 704at / bt ( center frequency , 7.5  mhz ) equipped with aplio xv / xg/500 ( toshiba medical systems corp . , seven segments of the gi tract were sequentially and individually assessed , including the stomach , duodenum , jejunum , ileum , rightsided colon , leftsided colon , and rectum . in this study , five registered medical sonographers in gastroenterology who had more than fiveyr experience performed us examinations . the thickest and widest parts in each segment were measured to determine the thickness and dilatation , respectively . abnormal thickening of the gi tract wall was defined as a thickness > 5  mm in the stomach and rectum , and > 3.5  mm in the small intestine and colon 11 , 12 , 13 . the thickness of internal low echoic layer reflecting inflammation of the mucosa , muscularis mucosa , and submucosa was measured as a representative of inflamed layer in the gi wall . dilatation of the intestine was defined as a diameter > 18  mm when filled with fluid 14 . measurements of the gastrointestinal ( gi ) tract wall . the thin echoic line in the middle of the internal echo poor layer reflects an interface layer between mucosa of the ventral and dorsal part of the gi tract . the thickest part is measured for the thickening of the gi tract wall ( a ) , the largest part for the diameter of the gi tract ( b ) , and the thickest part for the thickening of the internal low echoic layer ( c ) . color doppler imaging was concomitantly performed , with color gain adjusted until disappearance of noise for maximization of the sensitivity . color doppler frequency was set from 3.3 to 7.2  mhz , pulse repetition frequency from 4.7 to 10.1  cm / s , which was adjusted according to the type of probes and the depth of the lesion . increased doppler signaling was defined as spotty to linear color doppler signaling in mucosa and submucosa . it took about 520  min to assess entire gi tract by us , depending on the findings . us detects five layers of the normal gi tract wall 10 , 15 , 16 , 17 , 18 ( fig .  2 ) . we classified gigvhd into four grades according to the us findings of the five layers . the first layer corresponds to the border echo and a part of mucosa , the second layer is the rest of mucosa , the third layer is muscularis mucosa , submucosa , and a part of muscularis propria , the fourth layer is the rest of muscularis propria , and the fifth layer is serosa and border echo . a truepositive ( tp ) us corresponded to positive  us findings in patients with gigvhd . a truenegative ( tn ) us was defined by the absence of gi tract findings in patients without gigvhd . a falsenegative ( fn ) us corresponded to the absence of us abnormalities in patients with gigvhd . a falsepositive ( fp ) us corresponded to the findings of more than us grade 1 in patients without gigvhd . us findings and reference diagnosis methods of acute gigvhd were compared using sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) . the correlation between the stage of gigvhd and each us finding was evaluated by spearman 's rank correlation coefficient analysis . statistical analyses were performed using standard statistical software ( ibm spss statistics version 20.0 for mac os , chicago , il , usa ) . us was performed in 81 patients at a median of 28  ( range 3842 )  d after allogenic hsct ( table  1 ) . gigvhd was histologically confirmed by endoscopic examination in 23 patients , while it was clinically diagnosed in the remaining nine patients . numbers of patients with stage 1 , 2 , 3 , and 4 gigvhd were 14 , 5 , 3 , and 10 , respectively . fortynine patients did not have gigvhd ; 26 patients had enteritis not caused by gigvhd ; and 23 patients did not have any gi symptoms . patient characteristics bmt , bone marrow transplantation ; pbsct , peripheral blood stem cell transplantation ; cbt , cord blood transplantation ; gigvhd , gastrointestinal graftversushost disease . thickening of the ileum wall was observed in 23 ( 74% ) patients with gigvhd and was the  most common us finding of gigvhd ( table  2 ) . the second most common finding was the thickening of the colon wall in 57% patients , followed by thickening of the stomach wall , jejunum wall and rectum wall , and duodenum wall in 56% , 40% , and 29% patients , respectively . the average number of affected segments was 3 , ranging from 1 to 7 segments . dilatation of the rightsided colon , leftsided colon , jejunum , and ileum was observed in 36% , 29% , 18% , and 16% , respectively . increased echogenicity of the fat tissue surrounding the thickened bowel wall was observed in 17 ( 61% ) of 28 patients evaluated . increased doppler signaling in the mucosa and submucosa of the gi tract wall was demonstrated in 14 ( 56% ) of 25 patients with gigvhd evaluated . absence of peristalsis was observed in two ( 6% ) patients , and mucosal peeling in the internal lumen of the intestine was observed as doublelined inner layer in one ( 3% ) patient . comparison of ultrasonography ( us ) findings between gastrointestinal graftversushost disease ( gigvhd ) patients and non gigvhd patients p  <  0.05 , gigvhd patients were compared to nongvhd enteritis and no gigvhd symptoms ( tukey 's honestly significant difference test ) . the intestinal wall is thickened , and internal layer is markedly low in the jejunum ( fig .  3a ) and ascending colon ( fig . 3d ) . typical ultrasonography ( us ) findings in patients with gastrointestinal graftversushost disease ( gigvhd ) . ( a ) the jejunum wall is thickened ( arrow ) and internal low echoic layer is markedly low ( arrow head ) . degree of the wall thickening and dilatation of the gi tract , number of affected segments , and presence of ascites were not correlated with the clinical stage of gigvhd ( table  3 ) . on the other hand , the thickness of the internal low echoic layer , the echogenicity of mesenteric fat tissue , and the intensity of doppler signaling were significantly correlated with clinical stage of gigvhd ( table  3 ) . an association between the thickness of the internal low echoic layer and clinical stage of gigvhd is shown in fig . correlations between ultrasonography ( us ) findings and clinical gastrointestinal graftversushost disease ( gigvhd ) stage correlations between the thickness of internal low echoic layer and clinical gastrointestinal graftversushost disease ( gigvhd ) stage . a significant correlation is found between the thickness of internal low echoic layer and clinical gigvhd stage . among five layers in the gi wall , both mucosa and submucosa were preferentially involved in gigvhd , and their echo level became lower than normal as the severity of gigvhd increases . therefore , we classified us findings of gigvhd into four grades according to the us findings ( fig .  5 ) . us grade 1 was defined as slight wall thickening with preserved boundary between internal low echoic layer ( mucosa ) and submucosa ( fig . us grade 3 shows wall thickening with low echoic internal layer , involving mucosa and submucosa with an increased doppler signaling ( fig . us grade 4 shows mucosal epithelium pealing in the internal lumen or dilatation of intestine filled with fluid or absence of peristalsis ( fig . there was a significant correlation between the clinical stage of gigvhd and the us grade ( table  3 ) . ( a ) us grade 1 : mucosa and submucosal layers are slightly thickened in the wall layer ( arrow ) and the boundary between internal low echoic layer ( mucosa ) and the third layer is clear ( arrow head ) . ( b ) us grade 2 : diffuse wall thickness ( arrow ) and the boundary of internal low echoic layer and submucosa is obscure ( arrow head ) . ( c ) us grade 3 : internal low echoic layer is markedly low , and increased doppler signaling is seen in the layer ( arrow ) . ( d ) us grade 4 : desquamated mucosal epithelium ( arrow head ) is seen in the internal lumen with wall thickening ( arrow ) . followup us studies in 22 patients with gigvhd showed improvement of the abnormalities in patients successfully treated with methylprednisolone ( mpsl ) , but in none of the nonresponding patients . representative us findings of a patient successfully treated are shown in fig .  6 . at the onset of gigvhd , ct scanning showed wall thickening and dilatation of the colon and small intestine with air  fluid levels , suggesting paralytic ileus ( fig . ( a ) computed tomography ( ct ) scan shows thickening of the wall of the small intestine and colon . ( f ) us shows decreased thickening of the transverse colon wall . in 26 patients with nongvhd enterocolitis , abnormal us findings such as wall thickening and luminal dilatation were limited to narrow lesions ( table  2 ) . in patients not having intestinal symptoms , these us abnormalities were rarely detected . increased doppler signaling and echogenicity of mesenteric fat tissue were exclusively observed in patients with gigvhd . tp , fp , fn , and tn were 32 , 11 , 0 , and 38 , respectively ( table  4 ) . sensitivity , specificity , ppv , and npv of us for the diagnosis of gigvhd were 100% , 78% , 74% , and 100% , respectively . performance of ultrasonography for the diagnosis of gastrointestinal graftversushost disease ( gigvhd ) ppv , positive predictive value ; npv , negative predictive value . in fp cases , one patient had cmv colitis and showed diffuse wall thickening from the stomach to the ileum . the remaining nine patients had other causes of infection , and us findings were modest . in these fp cases , there was only one case showing an increase in doppler signaling or echogenicity of mesenteric fat tissue . our study demonstrated that diffuse wall thickness of the gi tract involving multiple segments was the most common finding in the patients with gigvhd and this finding help us to distinguish gigvhd from other causes of enteritis . this is probably due to more diffuse involvement of gi tract in gigvhd than other cases of enteritis . us abnormalities in these fp cases were milder and less extensive than those in patients with gigvhd , although diffuse and extensive wall thickening and dilatation of the colon were also reported in severe cases of cmv enterocolitis 19 , 20 . the strength of our study is high sensitivity ( 100% ) and npv ( 100% ) of us performance , suggesting that us is a useful tool  for helping diagnosis of gigvhd noninvasively . particularly , thickness of the internal low echoic layer suggesting inflammation in the mucosa and submucosa , degrees of the increased doppler signaling , echogenicity of mesenteric fat tissue , and us grades reflect clinical severity of gigvhd . on the other hand , gi tract wall thickness and luminal dilatation diagnosis of gigvhd is based on the observation of a spectrum of clinical symptoms and is often assisted by endoscopic examination and biopsy when the diagnosis is unclear . gi endoscopy is also utilized to map gigvhd lesions , but often difficult to perform in the presence of severe gi symptoms and assessment of the small intestine is difficult . in contrast , ct , us , and pet enable evaluation of entire gi tract noninvasively . typical ct and us findings of patients with gigvhd include luminal dilatation , thickening of the gi tract wall , air  fluid levels suggestive of paralytic ileus , and inflammatory thickening of fat tissue surrounding the involved gi tract 12 , 19 , 21 , 22 . pet is also useful for disease activity mapping 5 , 18 . among these modalities , us allows evaluation of the entire gi tract except for the esophagus , and b mode us and doppler study could detect inflammatory legions limited within certain wall layers that can not be detected by ct , mri , and pet . therefore , us is useful to map gigvhd lesions and to monitor the course of gigvhd after treatment . there are several limitations that should be taken into account when interpreting the findings , including the use of a retrospective design and small numbers of patients . prospective studies investigating a larger number of patients will be required to confirm our findings . while some difficulty would be concerned in delineating the gi tract of severely obese patients which we did not face in our study , it is anticipated that recent improvements in us technology that allow for greater penetration will overcome this limitation in future investigations . despite these limitations and while acknowledging the need for further research , the study provides evidence that us is an effective and efficient noninvasive means of identifying the sites and severity of the gi tract involved in gigvhd and monitoring response to treatment in patients with gigvhd . mn and tt designed the study and wrote the manuscript . as and te submitted the data and reviewed and completed the data as well as reviewed the results . ms , yk , so , th , ti , te , ai , and kh submitted the data .
abstractgastrointestinal graftversushost disease ( gigvhd ) is a major and lifethreatening complication of hematopoietic stem cell transplantation ( hsct ) . 
 this study evaluated the efficacy of ultrasonography ( us ) for assessing and monitoring gigvhd . 
 gi tract was evaluated by us in 81 patients . 
 us findings were positive in 43 patients , including 11 false positive , and negative in 38 patients . 
 sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of us for the diagnosis of gigvhd were 100% , 78% , 74% , 100% , and 86% , respectively . 
 diffuse wall thickening of the ileum was the most frequent finding in patients with gigvhd . 
 severity of gigvhd was correlated with the thickness of internal low echoic layer of the wall , the echogenicity of mesenteric fat tissue , and the intensity of doppler signaling . 
 we classified us findings of gigvhd into four us  grades . 
 there was a significant correlation between clinical stage of gigvhd and the us grade . 
 these ultrasonographic abnormalities were improved with clinical improvement of gigvhd upon treatment . 
 thus , us is an effective and efficient noninvasive means of identifying the extent and severity of gigvhd and monitoring response to treatment .