Clinical molecular imaging in intestinal graft-versus-host disease: mapping of disease activity, prediction, and monitoring of treatment efficiency by positron emission tomography

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2909-2918 ◽  
Author(s):  
Matthias Stelljes ◽  
Sven Hermann ◽  
Jörn Albring ◽  
Gabriele Köhler ◽  
Markus Löffler ◽  
...  

Gastrointestinal graft-versus-host disease (GVHD) is a common and potentially life-threatening complication after allogeneic hematopoietic stem-cell transplantation (HSCT). Noninvasive tests for assessment of GVHD activity are desirable but lacking. In the present study, we were able to visualize intestinal GVHD-associated inflammation in an allogeneic murine transplantation model by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in vivo. A predominant localization of intestinal GVHD to the colon was verified by histology and fluorescence reflectance imaging of enhanced green fluorescent protein (EGFP)–expressing donor cells. Colonic infiltration by EGFP+ donor lymphocytes matched increased FDG uptake in PET examinations. These preclinical data were prospectively translated into 30 patients with suspected intestinal GVHD beyond 20 days after transplantation. A total of 14 of 17 patients with a diagnostic histology showed significant FDG uptake of the gut, again predominantly in the colon. No increased FDG uptake was detected in 13 patients without histologic evidence of intestinal GVHD. Our findings indicate that FDG-PET is a sensitive and specific noninvasive imaging technique to assess intestinal GVHD, map its localization, and predict and monitor treatment responsiveness. Novel targeted tracers for PET may provide new insights into the pathophysiology of GVHD and bear the potential to further improve GVHD diagnosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3230-3230
Author(s):  
Matthias Stelljes ◽  
Jorn Albring ◽  
Sven Hermann ◽  
Christopher Poremba ◽  
Gabiele Kohler ◽  
...  

Abstract Gastrointestinal graft-versus-host disease (GI-GvHD) is a common and potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Detection of disease activity is pivotal for diagnosis and management of this condition. Despite methodical and technical limitations, histological analysis of endoscopically obtained specimens of the gut is still the gold standard in the diagnosis of GI-GvHD. Non-invasive objective tests for monitoring GvHD activity that cover the entire intestine are desirable but lacking. In the preclinical phase of our study, (C57BL/6 × BALB/c)F1 mice were transplanted with bone marrow and additional spleen cells (GvHD group) or with marrow grafts alone (control group) from allogeneic BALB/c donors. Serial measurements with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed a significant uptake of FDG in the GvHD group, predominantly of the colon. Histology of the whole gut revealed GvHD-associated inflammatory changes in the colon with normal findings in the small intestine. Analyses of the control group by FDG-PET, histology, and clinical assessment gave no evidence for GvHD. Bioluminescence imaging of the gut from F1 recipients transplanted from allogeneic C57BL/6-Tg(ACTB-EGFP) donors showed a significant infiltration, again predominantly of the colon, by EGFP positive donor cells and a matching FDG uptake in following PET examinations. In a subsequent clinical study, 22 patients with suspected GI-GvHD were examined by FDG-PET in combination with low-dose computed tomography (n=12) or by FDG-PET alone (n=10). Endoscopy of the rectum and sigmoid (n=13) or the entire colon (n=7) with assessment of mucosal specimens was performed in 20 patients. The two patients without endoscopic evaluation had normal FDG-PET results and showed normalisation of initial symptoms without further treatment. In addition, serial tests of stool for viral, bacterial or fungal infections and analyses of blood for CMV (pp65 and CMV-PCR), were without any pathological findings in all patients. In patients with proven GI-GvHD (progressive diarrhea, histology results conclusive for GvHD and positive FDG-PET results), therapy with corticosteroids was started, whereas in the absence of pathological findings no further therapy was given. Twelve of the 22 patients showed a significant FDG uptake of the gut, again predominantly in the colon. In all of these patients, GvHD responded to immunosuppressive treatment, and re-evaluation with FDG-PET showed markedly decreased FDG uptake in 6 out of 6 patients. None of the 10 patients with normal FDG-PET findings developed GvHD of the gut. The findings indicate that diagnostic imaging using FDG-PET with or without low-dose computed tomography is a sensitive, non-invasive procedure to assess localization and activity of GI-GvHD, with the potential for widespread clinical use following allogeneic HSCT.


2012 ◽  
Vol 39 (8) ◽  
pp. 1659-1665 ◽  
Author(s):  
TAKAYOSHI OWADA ◽  
REIKA MAEZAWA ◽  
KAZUHIRO KURASAWA ◽  
HARUTSUGU OKADA ◽  
SATOKO ARAI ◽  
...  

Objective.To evaluate the usefulness of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in the management of patients with inflammatory myopathy. We examined whether FDG-PET scanning detects myositis or extramuscular lesions in patients with polymyositis (PM) and dermatomyositis (DM).Methods.FDG-PET imaging was performed in 24 patients with active inflammatory myopathy (PM, 11; DM, 13). The images were read by radiologists in a blinded manner. FDG uptake into muscles was judged positive when the intensity of muscles was higher than or equal to that of the liver. As controls, FDG imaging findings of patients with a lung mass and without muscle diseases were used. To investigate associations between FDG-PET findings and clinical/laboratory findings, the patients’ medical records were reviewed retrospectively.Results.Increased FDG uptake in muscles was found in 8 of 24 (33%) patients. In 67 of 69 (97%) controls without muscle diseases, no muscle FDG uptake was detected. The sensitivity of FDG-PET to detect myositis was lower than that of electromyogram (EMG), magnetic resonance imaging, and muscle biopsy. There were no significant differences in clinical manifestations between patients with and without increased FDG uptake in muscles, although patients with FDG muscle uptake had a tendency to have extended myositis with endomysial cell infiltration. FDG-PET detected neoplasms in patients with associated malignancy. FDG uptake in lungs was found in 7 of 18 patients with interstitial lung disease.Conclusion.FDG-PET imaging has limited usefulness for the evaluation of myositis in patients with PM/DM because of its low sensitivity, although it might be useful for detection of malignancy in these patients.


2020 ◽  
Vol 27 (3) ◽  
pp. 509-515
Author(s):  
Erik Groot Jebbink ◽  
Leo H. van Den Ham ◽  
Beau B. J. van Woudenberg ◽  
Riemer H. J. A. Slart ◽  
Clark J. Zeebregts ◽  
...  

Purpose: To investigate the physiological uptake of hybrid fluorine-18-fluorodeoxyglucose (FDG)–positron emission tomography/computed tomography (PET/CT) before and after an uncomplicated endovascular aneurysm sealing (EVAS) procedure as a possible tool to diagnose EVAS graft infection and differentiate from postimplantation syndrome. Materials and Methods: Eight consecutive male patients (median age 78 years) scheduled for elective EVAS were included in the prospective study ( ClinicalTrials.gov identifier NCT02349100). FDG-PET/CT scans were performed in all patients before the procedure and 6 weeks after EVAS. The abdominal aorta was analyzed in 4 regions: suprarenal, infrarenal neck, aneurysm sac, and iliac. The following parameters were obtained for each region: standard uptake value (SUV), tissue to background ratio (TBR), and visual examination of FDG uptake to ascertain its distribution. Demographic data were obtained from medical files and scored based on reporting standards. Results: Visual examination showed no difference between pre- and postprocedure FDG uptake, which was homogenous. In the suprarenal region no significant pre- and postprocedure differences were observed for the SUV and TBR parameters. The infrarenal neck region showed a significant decrease in the SUV and no significant decrease in the TBR. The aneurysm sac and iliac regions both showed a significant decrease in SUV and TBR between the pre- and postprocedure scans. Conclusion: Physiological FDG uptake after EVAS was stable or decreased with regard to the preprocedure measurements. Future research is needed to assess the applicability and cutoff values of FDG-PET/CT scanning to detect endograft infection after EVAS.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4738-4738
Author(s):  
Masaaki Takatoku ◽  
Takahiro Nagashima ◽  
Toshihiko Sato ◽  
Tadashi Nagai ◽  
Norio Komatsu ◽  
...  

Abstract Usefulness of FDG-PET (positron emission tomography) in the discrimination between hypoplastic myelodysplastic syndromes and aplastic anemia Masaaki Takatoku, MD PhD1, Takahiro Nagashima, MD*1, Toshihiko Sato, MD*2, Tadashi Nagai, MD PhD1, Norio Komatsu, MD PhD1, Keiya Ozawa, MD PhD1 1Division of Hematology, Department of Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan; 2Utsunomiya Central Clinic, Utsunomiya, Tochigi, Japan It is sometimes difficult to distinguish hypoplastic myelodysplastic syndromes (MDS) from aplastic anemia (AA) using current diagnostic methods, such as bone marrow pathology and chromosome analysis. Although magnetic resonance imaging (MRI) is useful for diagnosis of MDS with hypercellular marrow, it is not easy to discriminate between hypoplastic MDS and AA using this method, because the high intensity pattern on T1 enhanced image is similar in these disorders. Recently, quantitative imaging with fluorine-18 fluorodeoxyglucose (FDG) PET has been recognized as a useful method for the discrimination between benign and malignant regions in various conditions. Because the decrease in the FDG-uptake at the late phase is much slower in malignant region than in benign region, dual time point imaging provides more accurate information than single time point scanning. In this study, we investigated the usefulness of dual time protocol FDG-PET in the differential diagnosis of hypoplastic MDS and AA. Six patients [2 with AA, 4 with MDS (including one hypoplastic MDS)] and 30 healthy adults agreed to participate in this study. Bone marrow biopsy, FDG- PET, MRI, and computed tomography (CT) were carried out, and a PET functional image was integrated into a CT anatomical image. The spine, femur and sternum lesions were detected by their increased 18F-FDG uptake at 60 and 120 min after injection of 0.12 mCi/kg of 18F-FDG. The maximum and mean lesional standardized uptake values (SUVmax and SUVmean) after 60 and 120 min were determined. The median SUVmax and SUVmean values of normal lumbar regions at 60 min were 1.94 ± 0.16 and 1.77 ± 0.11, respectively. In the MDS cases, those values at 60 min were 2.39 (range 2.12–2.72) and 2.06 (range 1.91–2.23), respectively. At 120 min, the median SUVmax and SUVmean values of normal cases were 1.33 ± 0.21 and 1.20 ± 0.16, respectively, whereas those of MDS cases were 2.42 (range 2.08–2.78) and 2.14 (range 1.50–2.26), respectively. Thus, the SUVmax and SUVmean values in MDS cases remained at high levels at 120 min in contrast to the decreased levels in normal cases. It is noteworthy that the SUVmax and SUVmean values of a hypoplastic MDS case were also high (2.21 and 2.01 at 60 min, 2.16 and 1.97 at 120 min), suggesting that bone marrow in MDS has a hyper metabolic state of glucose like other malignant disorders. We also observed patchy hot areas, which may be a visualization of ineffective hematopoiesis, throughout the spine image of hypoplastic MDS. In contrast, the SUVmax and SUVmean values of AA cases were 1.82 and 1.66 at 60 min and 1.31 and 1.19 at 120 min (case 1), 1.69 and 1.61 at 60 min and 1.30 and 1.13 at 120 min (case 2), indicating that there is no difference in the SUVmax and SUVmean values at the both time points between AA and normal cases. These results raised the possibility that the discrimination between hypoplastic MDS and AA, in which MRI shows a common observation, can be made using FDG-PET.


2001 ◽  
Vol 19 (15) ◽  
pp. 3516-3523 ◽  
Author(s):  
W. B. Eubank ◽  
D. A. Mankoff ◽  
J. Takasugi ◽  
H. Vesselle ◽  
J. F. Eary ◽  
...  

PURPOSE: To determine the prevalence of suspected disease in the mediastinum and internal mammary (IM) node chain by18fluorodeoxyglucose (FDG) positron emission tomography (PET), compared with conventional staging by computed tomography (CT) in patients with recurrent or metastatic breast cancer.PATIENTS AND METHODS: We retrospectively evaluated intrathoracic lymph nodes using FDG PET and CT data in 73 consecutive patients with recurrent or metastatic breast cancer who had both CT and FDG PET within 30 days of each other. In reviews of CT scans, mediastinal nodes measuring 1 cm or greater in the short axis were considered positive. PET was considered positive when there were one or more mediastinal foci of FDG uptake greater than the mediastinal blood pool.RESULTS: Overall, 40% of patients had abnormal mediastinal or IM FDG uptake consistent with metastases, compared with 23% of patients who had suspiciously enlarged mediastinal or IM nodes by CT. Both FDG PET and CT were positive in 22%. In the subset of 33 patients with assessable follow-up by CT or biopsy, the sensitivity, specificity, and accuracy for nodal disease was 85% , 90%, and 88%, respectively, by FDG PET; 54% , 85%, and 73%, respectively, by prospective interpretation of CT; and 50%, 83%, and 70%, respectively, by blinded observer interpretation of CT. Among patients suspected of having only locoregional disease recurrence (n = 33), 10 had unsuspected mediastinal or IM disease by FDG PET.CONCLUSION: FDG PET may uncover disease in these nodal regions not recognized by conventional staging methods. Future prospective studies using histopathology for confirmation are needed to validate the preliminary findings of this retrospective study.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4916-4916
Author(s):  
Masaaki Takatoku ◽  
Toshihiko Sato ◽  
Kaoru Hatano ◽  
Ken Omine ◽  
Masaki Mori ◽  
...  

Abstract Myelodysplastic syndromes (MDS) and aplastic anemia (AA) are classified bone marrow failure syndromes. Their clinical and pathological features partly overlap. It is sometimes difficult to distinguish hypoplastic MDS from AA by using current common diagnostic methods such as bone marrow biopsy and chromosome analysis. Although magnetic resonance image (MRI) is useful for diagnosis of MDS with hypercellular bone marrow, it is difficult to discriminate between hypoplastic MDS and AA using this method because the high intensity patterns on T1-enhanced images are similar in these disorders. Quantitative imaging with fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has been recognized as a useful examination for discrimination between benign and malignant regions in various conditions. Since the decrease in FDG uptake at the late phase is much slower in a malignant region than in a benign region, dual time point imaging provides more accurate information than does conventional single time point scanning. In this study, we investigated the usefulness of dual time protocol FDG-PET in differential diagnosis of hypoplastic MDS and AA. Seventeen patients (7 with typical MDS (RA), 4 with hypoplastic MDS, 6 with AA) and 30 healthy adults agreed to participate in this study. Bone marrow biopsy, FDG-PET, MRI and CT were carried out. Spine, femur and iliac lesions were detected by their increased FDG uptake at 60 and 120 min after injection of 0.12 mCi/kg of FDG. The mean lesional standardized uptake values (SUVmean) at 60 and 120 min after injection of FDG were determined. While the median SUVmean of normal lumbar regions at 60 min was 1.123 ± 0.219, that of MDS cases was 2.06 (range, 1.62–2.32). At 120 min, the median SUVmean of normal cases was 1.180 ± 0.119, whereas that of MDS cases was 2.44 (range, 2.08–2.98). It is noteworthy that the SUVmean of four hypoplastic MDS cases was also high (ranges: 1.96–2.23 at 60 min and 1.97–2.52 at 120 min), suggesting that bone marrow in hypoplastic MDS has a hyper-metabolic state of glucose like other malignant disorders. We also observed a patchy hot area, which may be a visualization of ineffective hematopoiesis, throughout the spine image of hypoplastic MDS. In contrast, the SUVmeans at both time points of four AA cases were not different from those in normal control cases. These results suggest that functional imaging analysis using an FDG-PET dual time protocol enables discrimination between hypoplastic MDS and AA, in which MR images similar intensities.


1998 ◽  
Vol 16 (5) ◽  
pp. 1770-1776 ◽  
Author(s):  
D J Macfarlane ◽  
V Sondak ◽  
T Johnson ◽  
R L Wahl

PURPOSE To assess prospectively the accuracy of 2-[l8F]-2-deoxy-D-glucose positron emission tomography (FDG-PET) for predicting regional node involvement in cutaneous malignant melanoma (CMM). PATIENTS AND METHODS Twenty-three patients with CMM (primary lesions > 1.5 mm thick) scheduled for lymph node dissection (LND) were preoperatively studied with FDG-PET. Thirteen patients underwent therapeutic LND of 14 node basins, while nine patients had elective LND of 10 node basins. Medical problems precluded surgery in one patient. Two observers unaware of the clinical node status-apart from whether a recent surgical scar was present-read attenuation-corrected reconstructed transverse images acquired between 50 and 60 minutes after injection. Intensity of FDG uptake was scored as 0 to 3 + on a semiquantitative four-point scale: 0, no uptake; 1 +, faint; 2 +, moderate; and 3 +, intense uptake. A node group was considered positive on FDG-PET if it contained at least one focus of FDG uptake of > or = 2+ intensity. Histopathologic examination of the 24 dissected node groups served as a reference. RESULTS Considering regional node basins, PET imaging demonstrated 11 true-positive (TP), 10 true-negative (TN), two false-negative (FN), and one false-positive (FP) result, for an overall accuracy of 88%. Histopathologic from one FN case showed seven malignant cells in a marginal node sinus. The FP was due to reactive changes postbiopsy. In one patient, clinically involved lymph nodes were correctly categorized TN by PET. At least four additional 2 + foci seen outside the dissected regions on PET may represent metastases and are being monitored. CONCLUSION FDG-PET accurately predicted regional node status in 88% of CMM cases. The failure to detect micrometastatic disease may be due to the limitations of the imaging equipment and technique used here.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yoshiyuki Ida ◽  
Hideyuki Tamai ◽  
Naoki Shingaki ◽  
Ryo Shimizu ◽  
Shuya Maeshima ◽  
...  

Abstract Background 18F-fluorodeoxyglucose (18F-FDG) uptake in hepatocellular carcinoma (HCC) is significantly associated with early recurrence and survival after curative surgical resection. However, there are no reports regarding the relationship between 18F-FDG uptake and outcomes after radiofrequency ablation (RFA). A prospective cohort study was conducted to evaluate the prognostic value of 18F-FDG positron emission tomography (PET) in HCC patients after RFA. Methods A total of 121 consecutive patients with primary HCC (≤3 tumors, of diameter ≤ 3 cm) without vascular invasion on imaging were examined by 18F-FDG-PET computed tomography prior to RFA. An HCC with a component of 18F-FDG uptake visibly stronger than that of surrounding liver was defined as 18F-FDG-PET positive. Results The median follow-up period was 1267 days. There were 110 18F-FDG-PET negative and 11 positive tumors. The cumulative 1-year recurrence rates in the 18F-FDG negative and positive groups were 30 and 64% (P = 0.017), respectively, and cumulative 1-year metastatic recurrence rates were 6 and 36% (P < 0.001), respectively. The cumulative 5-year survival rates were 88 and 22% (P < 0.001), respectively. Multivariate analysis revealed 18F-FDG-PET positivity and tumor size as independent factors related to metastatic recurrence and survival after RFA. Conclusions 18F-FDG-PET positivity was significantly associated with outcomes after RFA. RFA should not be readily selected as the first-line treatment for small HCC that includes a component of visually strong 18F-FDG uptake.


Blood ◽  
2020 ◽  
Vol 136 (4) ◽  
pp. 401-409
Author(s):  
Hind Rafei ◽  
Robert R. Jenq

Abstract Allogeneic hematopoietic stem cell transplantation (allo-SCT) offers cure for a variety of conditions, in particular, but not limited to, hematologic malignancies. However, it can be associated with life-threatening complications, including graft-versus-host disease (GVHD) and infections, which are factors limiting its widespread use. Technical advances in the field of microbiome research have allowed for a better understanding of the microbial flora of the human intestine, as well as dissection of their interactions with the host immune system in allo-SCT and posttransplant complications. There is growing evidence that the commensal microbiome is frequently dysregulated following allo-SCT and that this dysbiosis can predispose to adverse clinical outcomes, especially including acute intestinal GVHD and reduced overall survival. In this review, we discuss the interactions between the microbiome and the components of the immune system that play a major role in the pathways leading to the inflammatory state of acute intestinal GVHD. We also discuss the microbiome-centered strategies that have been devised or are actively being investigated to improve the outcomes of allo-SCT patients in regard to acute intestinal GVHD.


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