Redox reaction and clinical outcome of primary diffuse large B-cell lymphoma of the central nervous system: Prognostic role of metabolic and textural parameters of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/computed tomography in a small patient cohort.

OBJECTIVE: This study aimed to clarify the relationship between tumor redox reaction evaluated by Cu-diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) PET/computed tomography (CT) and disease-free survival (DFS) in patients with primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS). METHODS: Fifteen consecutive patients with histologically confirmed DLBCL-CNS underwent preoperative Cu-ATSM PET/CT and F-fluorodeoxyglucose (FDG) PET/CT. Statistical features of seven first-order parameters, including the standardized uptake value (SUV); 12 second-order parameters, including gray-level co-occurrence matrices and gray-level zone size matrices; and 5 high-order parameters, including neighborhood gray-tone difference matrices, were calculated from the volume of interest. We compared DFS with parameters, including SUVmax and tumor-to-background (T/B) ratio of FDG, and SUVmax, T/B ratio, and other textural features of Cu-ATSM. RESULTS: The mean follow-up duration after PET/CT was 458 (range, 41-1071) days. The SUVmax of FDG was significantly higher than that of Cu-ATSM (P = 0.001), but the T/B ratio was not significantly different between the scans (3.49 ± 2.29 vs 2.48 ± 1.18; P = 0.244). A Mantel-Cox log-rank test revealed no significant association between SUVmax of FDG and DFS (P = 0.641). A high SUVmax of Cu-ATSM had a tendency of shorter DFS (P = 0.055). Total lesion reduction, reductive tumor volume, and T/B ratio of Cu-ATSM were significantly correlated with poor DFS by univariate analysis (P = 0.049, 0.031, and 0.007, respectively). Neighborhood gray-level co-occurrence matrix dissimilarity was significantly correlated with poor DFS (P = 0.015). CONCLUSIONS: Metabolic and textural features derived from pretreatment Cu-ATSM PET/CT could be used for predicting DFS and establishing a novel treatment strategy in DLBCL-CNS patients.

Tumor Identification of Less Aggressive or Indolent Lymphoma With Whole-Body 11C-Acetate PET/CT.

PURPOSE: The aim of this study was to investigate the diagnostic performance of whole-body [C]acetate PET/CT in less aggressive or indolent lymphomas, wherein [F]FDG PET/CT would exhibit limited sensitivity. METHODS: Between September 2016 and May 2018, we prospectively evaluated 17 patients (9 men, 8 women; mean age [range], 71 [45-87] years) with pathologically proven less aggressive or indolent lymphomas according to Non-Hodgkin's Lymphoma Classification Project, using both [F]FDG PET/CT and [C]acetate PET/CT (performed on the same day). Detected nodal lesions were recorded according to the Ann Arbor classification. Extranodal (EN) lesions were also evaluated. We compared whole-body lesion detection between [F] FDG PET/CT and [C]acetate PET/CT using the McNemar test. RESULTS: In all patients, significantly more nodal and EN lesions were detected using [C]acetate PET/CT than [F]FDG PET/CT (nodal: 84 vs 64 regions; P < 0.001; EN: 26 vs 19 regions, P = 0.039). Bone lesions were detected in 8 and 5 patients using [C]acetate PET/CT and [F]FDG PET/CT, respectively (P = 0.25). Among the 14 patients (82.4%) who underwent bone marrow biopsy, bone marrow involvement was detected with sensitivities of 100% (6/6 patients) and 80% (5/6 patients) using [C]acetate PET/CT and [F]FDG PET/CT, respectively. Multiple areas of focal uptake in the spleen of 1 patient were exhibited on [F]FDG PET/CT but not [C]acetate PET/CT. CONCLUSIONS: [C]acetate PET/CT exhibited greater sensitivity than [F]FDG PET/CT for lesion detection in patients with less aggressive or indolent lymphomas, thus promising applicability as a physiological tracer in the study of such lesions.

Takayasu arteritis: clinical importance of extra-vessel uptake on FDG PET/CT.

BACKGROUND: [F-18]fluorodeoxyglucose positron emission tomography/computed tomography is routinely used for assessing Takayasu arteritis patients. However, extra-vessel [F-18]fluorodeoxyglucose uptake has not been evaluated in detail in these patients. We aimed to describe the extent and distribution of extra-vascular [F-18]fluorodeoxyglucose uptake on positron emission tomography/computed tomography in Takayasu arteritis patients. Seventy-three [F-18]fluorodeoxyglucose positron emission tomography/computed tomography scans from 64 consecutive Takayasu arteritis patients (59 women, mean age, 35.4 years; range, 13 to 71 years) and 40 scans from age-matched controls (36 women, mean age, 37.8 years; range, 13 to 70 years) were examined. We graded [F-18]fluorodeoxyglucose uptake in large vessels using a 4-point scale and evaluated extra-vessel findings. Factors correlated with disease activity were examined. We evaluated the relationship between disease activity according to the National Institutes of Health score with extra-vessel findings, as well as other inflammatory markers (e.g., white blood cell count and C-reactive protein level). RESULTS: Extra-vessel involvement was present in 50 of 73 (68.4%) scans, specifically at the following sites: lymph nodes, 1.4%; thyroid glands, 17.8%; thymus, 11.0%; spleen, 1.4%; vertebrae, 45.2%; and pelvic bones, 9.6%. Takayasu arteritis patients had higher [F-18]fluorodeoxyglucose uptake in the spine (P = 0.03) and thyroid glands (P = 0.003) than did controls; uptake in other regions was comparable between groups. Compared with inactive patients, those with active Takayasu arteritis had a higher number of [F-18]fluorodeoxyglucose uptake sites in the vasculature (P = 0.001). Finally, patients with a National Institutes of Health score of ≥ 1 had significantly higher extra-vascular involvement (P = 0.008). CONCLUSIONS: Extra-vessel [F-18]fluorodeoxyglucose uptake may be present in the context of Takayasu arteritis-related inflammatory processes. Information on extra-vascular [F-18]fluorodeoxyglucose uptake may be useful for detecting and evaluating inflammatory processes when interpreting positron emission tomography/computed tomography scans obtained from Takayasu arteritis patients.

Three-dimensional multimodality fusion imaging as an educational and planning tool for deep-seated meningiomas.

INTRODUCTION: The utility of surgical simulation with three-dimensional multimodality fusion imaging (3D-MFI) has been demonstrated. However, its potential in deep-seated brain lesions remains unknown. The aim of this study was to investigate the impact of 3D-MFI in deep-seated meningioma operations. MATERIAL AND METHODS: Fourteen patients with deeply located meningiomas were included in this study. We constructed 3D-MFIs by fusing high-resolution magnetic resonance (MR) and computed tomography (CT) images with a rotational digital subtraction angiogram (DSA) in all patients. The surgical procedure was simulated by 3D-MFI prior to operation. To assess the impact on neurosurgical education, the objective values of surgical simulation by 3D-MFIs/virtual reality (VR) video were evaluated. To validate the quality of 3D-MFIs, intraoperative findings were compared. The identification rate (IR) and positive predictive value (PPV) for the tumor feeding arteries and involved perforating arteries and veins were also assessed for quality assessment of 3D-MFI. RESULTS: After surgical simulation by 3D-MFIs, near-total resection was achieved in 13 of 14 (92.9%) patients without neurological complications. 3D-MFIs significantly contributed to the understanding of surgical anatomy and optimal surgical view (p < .0001) and learning how to preserve critical vessels (p < .0001) and resect tumors safety and extensively (p < .0001) by neurosurgical residents/fellows. The IR of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 100% and 92.9%, respectively. The PPV of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 98.8% and 76.5%, respectively. CONCLUSIONS: 3D-MFI contributed to learn skull base meningioma surgery. Also, 3D-MFI provided high quality to identify critical anatomical structures within or adjacent to deep-seated meningiomas. Thus, 3D-MFI is promising educational and surgical planning tool for meningiomas in deep-seated regions.

Prognostic implications of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/CT in patients with glioma.

OBJECTIVE: The potential of positron emission tomography/computed tomography using 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of 62Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHOD: 56 patients with glioma of World Health Organization grade 2-4 were enrolled. All participants had undergone both 62Cu-ATSM PET/CT and 18F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox's proportional hazards model. RESULTS: Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using 62Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using 62Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p < 0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using 62Cu-ATSM PET/CT showed significant difference of progression-free survival (p < 0.05). CONCLUSIONS: 62Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to 18F-FDG PET/CT.

Staging accuracy of pancreatic cancer: comparison between non-contrast-enhanced and contrast-enhanced PET/CT.

PURPOSE: Our aim was to clarify the diagnostic impact of contrast-enhanced (CE) (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) for staging of pancreatic cancer compared to non-CE PET/CT. METHOD AND MATERIALS: Between April 2006 and November 2009, a total of 95 patients (age range, 36-83 years [mean age, 67]) with primary pancreatic cancer underwent (18)F-FDG PET/CT examinations. Diagnostic accuracy was compared between non-CE PET/CT and CE PET/CT. Images were analyzed visually and quantitatively by two blinded reviewers. Reference standard was histological examination in 48 patients (51%) and/or confirmation of an obvious progression in number and/or size of the lesions on follow-up CT examinations in 47 patients (49%). RESULTS: For T-staging, invasion of duodenum (n=20, 21%), mesentery (n=12, 13%), and retroperitoneum (n=13, 14%) was correctly diagnosed by both modalities. The ROC analyses revealed that the Az values of celiac artery (CA), common hepatic artery (CHA), splenic artery (SV), and superior mesenteric vein (SMV) invasion were significantly higher in the CE PET/CT group for both readers. Nodal metastasis was correctly diagnosed by CE PET/CT in 38 patients (88%) and by non-CE PET/CT in 45 patients (87%). Diagnostic accuracies of nodal metastasis in two modalities were similar. Using CE PET/CT, distant metastasis, scalene node metastasis, and peritoneal dissemination were correctly assigned in 39 patients (91%), while interpretation based on non-CE PET/CT revealed distant metastasis, scalene node metastasis, and peritoneal dissemination in 42 patients (81%). Diagnostic accuracy of distant metastasis, scalene node metastasis, and peritoneal dissemination with CE PET/CT was significantly higher than that of non-CE PET/CT (p<0.05). CONCLUSION: CE PET/CT allows a more precise assessment of distant metastasis, scalene node metastasis, and peritoneal dissemination in patients with pancreatic cancer.

Tumor hypoxia and microscopic diffusion capacity in brain tumors: a comparison of (62)Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET/CT and diffusion-weighted MR imaging.

OBJECTIVES: The aim of this study was to clarify the relationship between tumor hypoxia and microscopic diffusion capacity in primary brain tumors using (62)Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) ((62)Cu-ATSM) PET/CT and diffusion-weighted MR imaging (DWI). METHODS: This study was approved by the institutional human research committee and was HIPAA compliant, and informed consent was obtained from all patients. (62)Cu-ATSM PET/CT and DWI were performed in a total of 40 primary brain tumors of 34 patients with low grade glioma (LGG, n = 13), glioblastoma (GBM, n = 20), and primary central nervous system lymphoma (PCNSL, n = 7). (62)Cu-ATSM PET/CT parameters and apparent diffusion coefficient (ADC) obtained by DWI were compared. RESULTS: High intensity signals by (62)Cu-ATSM PET/CT and DWI in patients with GBM and PCNSL, and low intensity signals in LGG patients were observed. An inverse correlation was found between maximum SUV (SUVmax) and minimum ADC (ADCmin) (r = -0.583, p < 0.0001), and between tumor/brain ratio (T/Bratio) and ADCmin for all tumors (r = -0.532, p < 0.0001). Both SUVmax and T/Bratio in GBM were higher than LGG (p < 0.0001 and p < 0.0001), and those in PCNSL were also higher than GBM (p = 0.033 and p = 0.044). The ADCmin was lower in GBM (p = 0.011) and PCNSL (p = 0.01) than in LGG, while no significant difference was found between GBM and PCNSL (p = 0.90). CONCLUSION: Tumor hypoxia assessed by (62)Cu-ATSM PET/CT correlated with microscopic diffusion capacity obtained by DWI in brain tumors. Both (62)Cu-ATSM PET/CT and DWI were considered feasible imaging methods for grading glioma. However, (62)Cu-ATSM PET/CT provided additional diagnostic information to differentiate between GBM and PCNSL.

Correlation of metabolic tumor volume and 11C-choline uptake with the pathology of prostate cancer: evaluation by use of simultaneously recorded MR and PET images.

PURPOSE: This study was conducted to assess the relationship between (11)C-choline uptake and pathologic findings obtained by combined use of magnetic resonance (MR) and positron emission tomography (PET) imaging of patients with prostate cancer. MATERIALS AND METHODS: We retrospectively evaluated 69 patients with prostate cancer who underwent (11)C-choline PET-CT and magnetic resonance imaging before radical prostatectomy. Combined MR-PET images were acquired to obtain precise anatomic information. The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) were compared with pathologic findings from resected specimens as the reference standard. RESULTS: The mean and standard deviation of tumor SUVmax and MTV were 3.9 ± 1.8 and 12.9 ± 16.4, respectively. Tumors with high MTV (≧8.2) were more likely to be admixed with prostatic intraepithelial neoplasia (PIN) (p < 0.0001) or hyperplasia (p < 0.0001) in the background than those without these findings. Multiple regression analysis also revealed that the presence of hyperplasia (OR; 4.25, 95% CI 1.25-14.4, p = 0.02) and PIN (OR; 9.22, 95% CI 2.60-32.7, p = 0.001) were associated with tumors with high MTV. CONCLUSION: We have demonstrated, by pathologic evaluation of patients with prostate cancer, that (11)C-choline uptake volume is greater for prostate cancer admixed with PIN and hyperplasia than that without.

Assessment of atherosclerosis in oncologic patients using ¹8F-fluoride PET/CT.

OBJECTIVES: The purpose of this study was to evaluate the prevalence, distribution, and relationship of (18)F-fluoride uptake and arterial calcification in oncologic patients using (18)F-fluoride PET/CT. METHODS: Image data obtained from 29 oncologic patients undergoing whole-body (18)F-fluoride PET/CT were evaluated retrospectively. Arterial wall (18)F-fluoride uptake and calcification were analyzed both quantitatively and semiquantitatively in 8 patients with arterial (18)F-fluoride uptake. RESULTS: Arterial (18)F-fluoride uptake was observed at 35 lesions in 8 (28 %) of the 29 patients, and calcification was observed at 345 lesions in the same patients. Five of the 8 patients had prostate cancer, and the remaining patients had hepatocellular carcinoma or malignant melanoma. In these 8 patients, the prevalence of both (18)F-fluoride uptake and calcification was highest in the abdominal aorta, followed by the descending thoracic aorta and the aortic arch. Colocalization of radiotracer accumulation and calcification could be observed in the 32 lesions (91 %) with arterial (18)F-fluoride uptake, and only the 3 lesions (9 %) with arterial (18)F-fluoride uptake were not colocalized with arterial calcification. The presence of both arterial radiotracer uptake and calcification was significantly associated with advancing age (P < 0.01). CONCLUSION: Our results suggest that (18)F-fluoride PET/CT might be a useful modality for detecting active mineral deposition sites of atherosclerosis in oncologic patients.

Role of 18F-fluoride PET/CT in the assessment of multiple myeloma: initial experience.

PURPOSE: The aim of this study was to report our early experience with (18)F-fluoride PET/CT for detecting lesions and evaluate the usefulness of this modality in the assessment of multiple myeloma (MM). MATERIALS AND METHODS: (18)F-fluoride PET/CT and (99m)Tc-MDP bone scintigraphy (BS) studies from 7 myeloma patients (4 male and 3 female, mean age 55 years) diagnosed according to standard criteria were reviewed retrospectively. Two reviewers visually and quantitatively analyzed the images and recorded their findings after reaching a consensus. Diagnostic certainty regarding the presence or absence of myeloma lesions was evaluated according to the reference standard consisting of whole-body magnetic resonance imaging and whole-body X-ray. RESULTS: A total of 93 affected areas were definite according to the reference standard. Of these, 83 affected areas (89 %) were identified on (18)F-fluoride PET/CT, whereas 54 affected areas (58 %) were found on BS. Mean SUVmax in the affected areas was 9.8 ± 3.2 (standard deviation) ranging from 5.0 to 21.2. A total of s17 lesions with bone fracture were also detected by (18)F-fluoride PET/CT and 2 lesions (12 %) were negative on BS. CONCLUSION: Our result showed that (18)F-fluoride PET was a possible modality to detect areas of lesions in patients with MM.

Age-related changes in pre- and postmenopausal women investigated with 18F-fluoride PET--a preliminary study.

OBJECTIVE: To evaluate the relationship between age and regional skeletal uptake at sites consisting of either predominantly trabecular or cortical bone using (18)F-fluoride positron emission tomography (PET) in pre- and postmenopausal women. MATERIALS AND METHODS: Thirty-two women (40.6 ± 12.3 years; age range 25-72 years) were assigned to one of two groups: group 1 comprised 22 premenopausal women (33 ± 6.5 years; age range 25-48 years) and group 2 comprised 10 postmenopausal women (56 ± 6.7 years; age range 49-72 years). The maximum standardized uptake value (SUVmax) was determined from the lumbar spine and the humeral shaft. Student's t-test for each unpaired dataset was used to evaluate statistical differences between the two groups. The SUVmax values for the humeral shaft and the lumbar spine were compared with aging. RESULTS: The SUVmax (mean ± SD) was 1.2 ± 0.5 in the humeral shaft and 4.7 ± 1.0 in the lumbar spine. The SUVmax in the humeral shaft correlated significantly with advancing age (r = 0.67, P < 0.01). The SUVmax in the lumbar spine declined significantly with advancing age (r = -0.50, P < 0.01). The humeral shaft of women in group 1 exhibited a significantly lower SUVmax compared to that in group 2 (1.1 ± 0.4 versus 1.6 ± 0.6; P < 0.05). On the other hand, the lumbar spine of women in group 1 exhibited a significantly higher SUVmax compared to that in group 2 (5.1 ± 0.7 versus 4.0 ± 1.1; P < 0.05). The mean SUVmax in the lumbar spine was 2.5 times greater than that in the humeral shaft in group 2. CONCLUSION: Semiquantitative analysis with (18)F-fluoride PET might be a useful tool for analyzing age-related changes in pre- and postmenopausal women.

F-18 FDG uptake patterns and disease activity of collagen vascular diseases-associated arthritis.

PURPOSE: The purpose of the present study was to investigate F-18 FDG uptake patterns, and to see whether joint F-18 FDG uptake reflected disease activity in patients with collagen vascular diseases (CVD)-associated arthritis. MATERIALS AND METHODS: A total of 72 patients with CVD-associated arthritis and 30 control subjects who underwent F-18 FDG PET or PET/CT were retrospectively investigated. PET images of 12 major joints, 7 minor joints, and extra-articular accumulation were assessed. We investigated F-18 FDG uptake patterns and the relationships between the degree of F-18 FDG uptake and distribution, clinical symptoms, and laboratory test results. RESULTS: Remitting seronegative symmetric synovitis with pitting edema syndrome, mixed connective tissue disease, rheumatoid arthritis, and systemic sclerosis tended to show strong and multiple joint F-18 FDG uptake. F-18 FDG uptake was found in bone marrow (86%) and/or spleen (57%) in 7 patients with adult-onset Still disease. The maximum standardized uptake value (SUVmax) correlated with the counts of erythrocyte sedimentation rate, matrix metalloproteinase-3, IgG, and IgA. Joint swelling had a positive association with SUVmax. Multiple logistic regression analyses revealed that factor associated with increased SUVmax of the joint was joint swelling (P = 0.005). CONCLUSIONS: The degree of joint F-18 FDG uptake may contribute to predict active inflammatory process of the joint. In addition, F-18 FDG uptake patterns may have a potential which helps differential diagnosis of CVD-associated arthritis.