Four-dimensional quantitative analysis using FDG-PET in clinical oncology.

Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has been commonly used in many oncological areas. High-resolution PET permits a three-dimensional analysis of FDG distributions on various lesions in vivo, which can be applied for tissue characterization, risk analysis, and treatment monitoring after chemoradiotherapy and immunotherapy. Metabolic changes can be assessed using the tumor absolute FDG uptake as standardized uptake value (SUV) and metabolic tumor volume (MTV). In addition, tumor heterogeneity assessment can potentially estimate tumor aggressiveness and resistance to chemoradiotherapy. Attempts have been made to quantify intratumoral heterogeneity using radiomics. Recent reports have indicated the clinical feasibility of a dynamic FDG PET-computed tomography (CT) in pilot cohort studies of oncological cases. Dynamic imaging permits the assessment of temporal changes in FDG uptake after administration, which is particularly useful for differentiating pathological from physiological uptakes with high diagnostic accuracy. In addition, several new parameters have been introduced for the in vivo quantitative analysis of FDG metabolic processes. Thus, a four-dimensional FDG PET-CT is available for precise tissue characterization of various lesions. This review introduces various new techniques for the quantitative analysis of FDG distribution and glucose metabolism using a four-dimensional FDG analysis with PET-CT. This elegant study reveals the important role of tissue characterization and treatment strategies in oncology.

Association between cerebrovasoreactivity and stroke in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Background: Impaired cerebrovasoreactivity is thought to play an important role in the pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to clarify the association between cerebrovascular reactivity and stroke in patients with CADASIL. Methods: We retrospectively recruited 14 patients with CADASIL, eight of whom had symptomatic stroke. They underwent quantitative single-photon emission computed tomography using an autoradiographic method at rest and after acetazolamide (ACZ) administration. Regional cerebral blood flow (rCBF) in the cerebral cortex, lenticular nucleus, thalamus, and cerebellum was measured. We compared the rCBF parameters between patients with and without stroke. Results: The baseline characteristics and magnetic resonance imaging findings were similar between the two groups, except for a higher frequency of pyramidal tract sign (75% vs. 0%) and a larger number of old lacunes (15.4 ± 8.8 vs. 2.2 ± 1.8) in the patients with stroke. Of the rCBF parameters measured, significantly lower flow (mL/100 g/min) was observed in ACZ-rCBF in the thalamus (35.6 ± 9.4 vs. 51.1 ± 7.6, p = 0.01) and ΔrCBF in the thalamus (10.6 ± 3.7 vs. 21.0 ± 7.9, p = 0.02) in the patients with stroke. Conclusion: Cerebrovasoreactivity in the thalamus was significantly associated with stroke in patients with CADASIL.

Comparison between dynamic whole-body FDG-PET and early-delayed imaging for the assessment of motion in focal uptake in colorectal area.

OBJECTIVES: Serial changes of focal uptake in whole-body dynamic positron emission tomography (PET) imaging were assessed and compared with those in early-delayed imaging to differentiate pathological uptake from physiological uptake in the colorectal area, based on the change in uptake shape. METHODS: In 60 patients with at least 1 pathologically diagnosed colorectal cancer or adenoma, a serial 3 min dynamic whole-body PET/computed tomography imaging was performed four times around 60 min after the administration of 18F-fluorodeoxyglucose (FDG) to create a conventional (early) image by summation. Delayed imaging was performed separately at 110 min after FDG administration. High focal uptake lesions in the colorectal area were visually assessed as "changed" or "unchanged" on serial dynamic imaging and early-delayed imaging, based on the alteration in uptake shape over time. These criteria on the images were used to differentiate pathological uptake from physiological uptake. RESULTS: In this study, 334 lesions with high focal FDG uptake were observed. Among 73 histologically proven pathological FDG uptakes, no change was observed in 69 on serial dynamic imaging and 72 on early-delayed imaging (sensitivity of 95 vs. 99%, respectively; ns). In contrast, out of 261 physiological FDG uptakes, a change in uptake shape was seen in 159 on dynamic PET imaging and 66 on early-delayed imaging (specificity of 61 vs. 25%, respectively; p < 0.01). High and similar negative predictive values for identifying pathological uptake were obtained by both methods (98 vs 99%, respectively). Thus, the overall accuracy for differentiating pathological from physiological FDG uptake based on change in uptake shape tended to be higher on serial dynamic imaging (68%) than on early-delayed imaging (41%; p < 0.01). CONCLUSIONS: Dynamic whole-body FDG imaging enables differentiation of pathological uptake from physiological uptake based on the serial changes in uptake shape in the colorectal area. It may provide greater diagnostic value than early-delayed PET imaging. Thus, this technique holds a promise for minimizing the need for delayed imaging.

Dynamic whole-body 18F-FDG PET for differentiating abnormal lesions from physiological uptake.

PURPOSE: Serial assessment of visual change in 18F-FDG uptake on whole-body 18F-FDG PET imaging was performed to differentiate pathological uptake from physiological uptake in the urinary and gastrointestinal tracts. METHODS: In 88 suspected cancer patients, serial 3-min dynamic whole-body PET imaging was performed four times, from 60 min after 18F-FDG administration. In dynamic image evaluation, high 18F-FDG uptake was evaluated by two nuclear medicine physicians and classified as "changed" or "unchanged" based on change in uptake shape over time. Detectability of pathological uptake based on these criteria was assessed and compared with conventional image evaluation. RESULTS: Dynamic whole-body PET imaging provided images of adequate quality for visual assessment. Dynamic image evaluation was "changed" in 118/154 regions of high physiological 18F-FDG uptake (77%): in 9/19 areas in the stomach (47%), in 32/39 in the small intestine (82%), in 17/33 in the colon (52%), and in 60/63 in the urinary tract (95%). In the 86 benign or malignant lesions, 84 lesions (98%) were "unchanged." A high 18F-FDG uptake area that shows no change over time using these criteria is highly likely to represent pathological uptake, with sensitivity of 97%, specificity of 76%, PPV of 70%, NPV of 98%, and accuracy of 84%. CONCLUSION: Dynamic whole-body 18F-FDG PET imaging enabled differentiation of pathological uptake from physiological uptake in the urinary and gastrointestinal tracts, based on visual change of uptake shape.

Early effects of transcatheter aortic valve replacement on cardiac sympathetic nervous function assessed by 123I-metaiodobenzylguanidine scintigraphy in patients with severe aortic valve stenosis.

PURPOSE: The effects of transcatheter aortic valve replacement (TAVR) on cardiac sympathetic nervous (CSN) function have not been fully explored. This study aimed to investigate the early (within 2 weeks) effects of TAVR on CSN function in patients with severe aortic valve stenosis (AS) using 123I-metaiodobenzylguanidine (MIBG) scintigraphy. METHODS: Of 143 consecutive patients who were scheduled to undergo TAVR, 67 (18 men; median age 86 years) were evaluated in this single-centre prospective observational study. MIBG scintigraphy was performed at baseline and 3-14 days after the TAVR procedure to evaluate the heart-mediastinum ratio (H/M) and washout rate (WR). Differences between baseline and post-TAVR MIBG parameters were analysed. MIBG parameter changes were compared with echocardiographic parameters. Furthermore, factors involved in the improvement in MIBG parameters were investigated. RESULTS: All patients successfully underwent TAVR with improved echocardiographic parameters, including aortic valve area (AVA; 0.6 cm2 vs. 1.6 cm2), peak velocity (4.5 m/s vs. 2.0 m/s), mean pressure gradient (50 mmHg vs. 9 mmHg), and left ventricular ejection fraction (56% vs. 62%) (all p < 0.001). On MIBG imaging, delayed H/M significantly increased (2.57 vs. 2.68, p < 0.001), whereas WR decreased (32.2% vs. 26.8%, p < 0.001). In multivariate analysis, higher baseline WR was associated with improvement in WR (> 3%). Female sex, Clinical Frailty Scale score ≤ 5, baseline estimated glomerular filtration rate, and baseline AVA were predictors of improvement in delayed H/M (> 0.1). Baseline AVA and E/E' were independent predictors of improvement in both WR and delayed H/M. CONCLUSIONS: The CSN function was impaired in patients with AS, as assessed using MIBG scintigraphy. WR and delayed H/M improved immediately after TAVR. Improvement in CSN function may be related to echocardiographic AS severity at baseline before TAVR.

Increased 18F-FDG accumulation in the tonsils after chemotherapy for pediatric lymphoma: a common physiological phenomenon.

OBJECTIVE: Increased 18F-fluorodeoxyglucose (FDG) uptake in the tonsils after the completion of chemotherapy in patients with lymphoma may be misdiagnosed as tumor recurrence. This study aimed to investigate the changes in physiological FDG uptake in the tonsils during and after chemotherapy in pediatric patients with lymphoma. METHODS: A total of 47 FDG-PET/CT scans acquired from 13 pediatric patients with lymphoma (before chemotherapy [preC] = 9; during chemotherapy [durC] = 12; within 1 month after the end of chemotherapy [endC] = 11; and after achieving complete response [postC] = 15) were retrospectively included in this study. FDG uptake in the palatine tonsils was assessed using maximum standardized uptake value (SUVmax). The relative size of the palatine tonsils was calculated as the tonsil-pharyngeal ratio (TPR). Serial changes in the SUVmax and TPR were evaluated. RESULTS: The mean SUVmax was 3.7 ± 1.7, 2.6 ± 0.7, 2.3 ± 0.8, and 6.2 ± 1.6, at the preC, durC, endC, and postC scans, respectively (p < 0.0001); TPR was 59.0 ± 11.2%, 58.3 ± 9.4%, 54.4 ± 7.9%, and 62.2 ± 12.0% in these groups, respectively, with no significant inter-group differences. TPR and SUVmax showed no correlation. CONCLUSIONS: Increased physiological FDG uptake in the tonsils is commonly observed after the completion of chemotherapy, even in the absence of reactive hypertrophy.

Diagnostic Value of Muscle [11C] PIB-PET in Inclusion Body Myositis.

Background: The accumulation of multiple-protein aggregates within muscle fibers is a pathological hallmark of sporadic inclusion body myositis (s-IBM) with the presence of inclusion bodies. Amyloid-beta is one of the accumulated proteins in s-IBM. The aim of this study was to elucidate the utility of Pittsburgh compound B-positron emission tomography (PIB-PET) for diagnosing s-IBM. Methods: Nine patients with s-IBM and four patients with idiopathic inflammatory myopathy (IIM) were included. Patients underwent PIB-PET of body muscles. Standardized uptake values (SUVs) were measured in 16 muscles. A comparison of SUVs was made between s-IBM and IIM groups. The correlation between PIB-PET and clinical parameters was analyzed. Results: The mean SUV of all muscles in s-IBM patients was higher than in IIM patients (0.32 vs. 0.25, respectively; p = 0.031). Subgroup analysis identified a clear difference in SUVs of the forearm and lower-leg muscle groups (p = 0.021 and p = 0.045, respectively). There was no correlation between SUVs and clinical parameters in s-IBM patients. Conclusions: Muscle PIB-PET may help to make a diagnosis of s-IBM.

Active Bone Marrow With Focal FDG Accumulation Mimicking Bone Metastasis With a Case of Early Esophageal Cancer.

A 68-year-old man underwent F-FDG PET/CT for the staging of esophageal carcinoma discovered by a medical checkup. Increased focal accumulation in some vertebrae, right humerus, and right femoral bone was noted on FDG-PET, whereas CT showed relatively high attenuation, and MRI showed hypointense lesions on T1- and T2-weighted imaging. A bone biopsy revealed mildly hypercellular bone marrow in the thoracic spine with FDG accumulation and markedly hypocellular bone marrow in the pelvic bone without an increased uptake. InCl scintigraphy showed a similar distribution and confirmed the diagnosis of bone marrow reconversion.

Usefulness of the convexity apparent hyperperfusion sign in 123I-iodoamphetamine brain perfusion SPECT for the diagnosis of idiopathic normal pressure hydrocephalus.

OBJECTIVE: The gold standard for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is the CSF removal test. For elderly patients, however, a less invasive diagnostic method is required. On MRI, high-convexity tightness was reported to be an important finding for the diagnosis of iNPH. On SPECT, patients with iNPH often show hyperperfusion of the high-convexity area. The authors tested 2 hypotheses regarding the SPECT finding: 1) it is relative hyperperfusion reflecting the increased gray matter density of the convexity, and 2) it is useful for the diagnosis of iNPH. The authors termed the SPECT finding the convexity apparent hyperperfusion (CAPPAH) sign. METHODS: Two clinical studies were conducted. In study 1, SPECT was performed for 20 patients suspected of having iNPH, and regional cerebral blood flow (rCBF) of the high-convexity area was examined using quantitative analysis. Clinical differences between patients with the CAPPAH sign (CAP) and those without it (NCAP) were also compared. In study 2, the CAPPAH sign was retrospectively assessed in 30 patients with iNPH and 19 healthy controls using SPECT images and 3D stereotactic surface projection. RESULTS: In study 1, rCBF of the high-convexity area of the CAP group was calculated as 35.2­43.7 ml/min/100 g, which is not higher than normal values of rCBF determined by SPECT. The NCAP group showed lower cognitive function and weaker responses to the removal of CSF than the CAP group. In study 2, the CAPPAH sign was positive only in patients with iNPH (24/30) and not in controls (sensitivity 80%, specificity 100%). The coincidence rate between tight high convexity on MRI and the CAPPAH sign was very high (28/30). CONCLUSIONS: Patients with iNPH showed hyperperfusion of the high-convexity area on SPECT; however, the presence of the CAPPAH sign did not indicate real hyperperfusion of rCBF in the high-convexity area. The authors speculated that patients with iNPH without the CAPPAH sign, despite showing tight high convexity on MRI, might have comorbidities such as Alzheimer's disease.

New semi-quantitative 123I-MIBG estimation method compared with scoring system in follow-up of advanced neuroblastoma: utility of total MIBG retention ratio versus scoring method.

OBJECTIVE: The purpose of this study is to evaluate a new semi-quantitative estimation method using (123)I-MIBG retention ratio to assess response to chemotherapy for advanced neuroblastoma. METHOD: Thirteen children with advanced neuroblastoma (International Neuroblastoma Risk Group Staging System: stage M) were examined for a total of 51 studies with (123)I-MIBG scintigraphy (before and during chemotherapy). We proposed a new semi-quantitative method using MIBG retention ratio (count obtained with delayed image/count obtained with early image with decay correction) to estimate MIBG accumulation. We analyzed total (123)I-MIBG retention ratio (TMRR: total body count obtained with delayed image/total body count obtained with early image with decay correction) and compared with a scoring method in terms of correlation with tumor markers. RESULT: TMRR showed significantly higher correlations with urinary catecholamine metabolites before chemotherapy (VMA: r(2) = 0.45, P < 0.05, HVA: r(2) = 0.627, P < 0.01) than MIBG score (VMA: r(2) = 0.19, P = 0.082, HVA: r(2) = 0.25, P = 0.137). There were relatively good correlations between serial change of TMRR and those of urinary catecholamine metabolites (VMA: r(2) = 0.274, P < 0.001, HVA: r(2) = 0.448, P < 0.0001) compared with serial change of MIBG score and those of tumor markers (VMA: r(2) = 0.01, P = 0.537, HVA: 0.084, P = 0.697) during chemotherapy for advanced neuroblastoma. CONCLUSION: TMRR could be a useful semi-quantitative method for estimating early response to chemotherapy of advanced neuroblastoma because of its high correlation with urine catecholamine metabolites.

Utility of additional delayed post-therapeutic ¹³¹I whole-body scanning in patients with thyroid cancer.

OBJECTIVE: The purpose of this study is to compare early (3 days after administration) and delayed (7-9 days after administration) post-therapeutic ¹³¹I scanning for detecting metastatic lesions from differentiated thyroid carcinoma. METHODS: This study included 24 patients (10 men and 14 women) with differentiated thyroid carcinoma who underwent early and delayed whole-body scanning after ¹³¹I treatment. The early and delayed scan images were visually analyzed, and the region-to-whole-body ratio (RBR) and its variation from the early to delayed scanning (RBR variation) were calculated. RESULTS: In the visual analysis, lung metastases in 2 patients and 1 bone metastasis could not be detected on early scanning but were classified as moderate uptake on delayed scanning. The abdomen showed definite uptake on early scanning but was washed out on delayed scanning. The RBR variation of the lung and bone metastases was significantly higher than those of the abdomen and thyroid remnants. This suggests that the distribution of ¹³¹I was more quickly washed out of the abdomen and thyroid remnants than from the metastatic lesions. CONCLUSIONS: Delayed scanning showed a higher detection rate of lung and bone metastases than early scanning because of the washout of the physiological distributions. Additional delayed scanning is recommended, especially for high-risk patients with intensive physiological distribution on early scanning.

Simultaneous impairment of intracranial and peripheral artery vasoreactivity in CADASIL patients.

BACKGROUND: Reduced cerebrovascular reactivity (CVR) is an important step in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The present study utilized quantitative single photon emission computed tomography (SPECT) with the autoradiographic (ARG) method and reactive hyperemia peripheral arterial tonometry (RH-PAT) to assess vasoreactivity in intracranial arteries and in peripheral arteries in patients with CADASIL. METHODS: Quantitative SPECT studies were conducted in eight patients with CADASIL, while RH-PAT analysis was conducted in eight CADASIL patients and in eight age-matched normal subjects. Quantitative SPECT studies with the ARG method were performed at baseline and after administration of acetazolamide. Regional cerebral blood flow (rCBF) values were measured using stereotactic extraction estimation (SEE) methods. The rCBF of CADASIL patients was averaged in the bilateral frontal, temporal, parietal, and occipital lobes as well as in the limbic system, cerebellar hemisphere, whole cerebral cortex and basal ganglia. The CVR index from acetazolamide stress of intracranial arteries was calculated in each area. Vasoreactivity of peripheral arteries was estimated by the reactive hyperemia index (RHI) measured with a PAT device before and after interruption of arterial flow. RESULTS: Average RHI after post-deflation was lower in CADASIL patients than in normal subjects. RHI correlated significantly with CVR in all brain areas in CADASIL patients. CONCLUSIONS: Vasoreactivity is reduced in peripheral arteries and in intracranial arteries in patients with CADASIL.

Diaphragmatic hernia after radiofrequency ablation for hepatocellular carcinoma.

We describe a 71-year-old woman with a hepatocellular carcinoma who underwent percutaneous radiofrequency ablation (RF) with a single internally cooled electrode under computed tomography (CT) fluoroscopic guidance. Nine months after the procedure, CT images showed herniation of the large intestine into the right pleural cavity. To our knowledge this complication of RF performed with a single internally cooled electrode under CT guidance has not been previously reported.

Optimum b value for resolving crossing fibers: a study with standard clinical b value using 1.5-T MR.

INTRODUCTION: We sought to investigate the optimum b value for resolving crossing fiber using high-angular resolution diffusion imaging (HARDI)-based multi-tensor tractography. The study tested the standard b values that are commonly used in the routine clinical setting. METHODS: Ten normal volunteers (five men and five women) with a mean age of 26.3 years (range, 22-32 years) were scanned using a 1.5-T clinical magnetic resonance unit. Single-shot echo-planar imaging was used for diffusion-weighted imaging with a diffusion-sensitizing gradient in 32 orientations. The b values of 700, 1,400, 2,100, and 2,800 s/m(2) were used. Data postprocessing was performed using multi-tensor methods. The depiction of the optic nerves, optic tracts, and decussation of superior cerebellar peduncles were assessed. RESULTS: The depictions of the nerve fibers were independent of the b values tested. CONCLUSION: The depiction of crossing fibers by HARDI-based multi-tensor tractography is not substantially influenced by b values ranging from 700 to 2,800 s/m(2). Thus, the optimum b value within this range may be the lowest one considering the higher signal to noise ratio.

Intense F-18 FDG accumulation in idiopathic tumoral calcinosis.

An elderly Japanese woman presented to our hospital with a 5-month history of a growing mass on her right cheek. She did not complain of local pain, headache, hearing difficulty, or tinnitus. CT and MRI showed a dense calcified mass and F-18 fluorodeoxyglucose (FDG) PET demonstrated intense accumulation in the mass. Resection of the mass was performed and it was histologically diagnosed as idiopathic tumoral calcinosis.

Is it possible to define salvageable ischemic penumbra using semiquantitative rCBF levels derived from MR perfusion-weighted imaging?

INTRODUCTION: The purpose of this study was to test if magnetic resonance (MR) perfusion-weighted imaging (PWI) can reliably characterize the ischemic penumbra. MATERIALS AND METHODS: Sixteen patients with nonlacunar ischemic stroke who were scanned within 24 h after onset of symptoms were selected for the study. In previous studies, the level of regional cerebral blood flow (rCBF) in the normal white matter of the contralateral hemisphere was defined as 22 ml/100 g/min. We used this level as a standard of reference. We hypothesized that rCBF below this level would be amenable to infarct. The lesion-to-white matter ratios of rCBF were measured in the regions of ischemic core ("Core"), infarcted penumbra ("Growth"), salvaged penumbra ("Reversed"), and contralateral normal cortex ("Normal"). RESULTS: The rCBF of "Growth" and "Reversed" areas showed substantial overlap, which hampered the delineation of areas that would become infarcted. CONCLUSION: The semiquantitative rCBF derived from MR PWI may not accurately characterize the ischemic penumbra.

Effect of vascular stenosis on perfusion-weighted imaging; differences between calculation algorithms.

PURPOSE: To determine the most suitable postprocessing technique for magnetic resonance (MR) perfusion imaging in patients with vascular stenosis, by comparing the cerebral blood flow (CBF) maps of single photon emission tomography (SPECT) and perfusion MR imaging (MRI). MATERIALS AND METHODS: In 15 consecutive patients (14 men and one woman, mean age 73.9 +/- 6.0 years) with stenosis of common carotid artery (CCA) or internal carotid artery (ICA) of more than 75%, both brain perfusion MRI and brain perfusion SPECT were performed. From perfusion MR images, CBF maps were calculated with the first moment, singular value decomposition (SVD), and block circulant SVD (b-SVD) methods, and CBF maps from each algorithm were compared with those from SPECT. RESULTS: The b-SVD method had the best correlation with SPECT (R = 0.814), followed by the first moment method (R = 0.776) and the SVD method (R = 0.723). The b-SVD method has the least mean difference with SPECT (0.118), the first moment method also had less difference (0.121), and the SVD had greatest mean difference (0.164). CONCLUSION: Our results suggest that in patients with vascular impairment the b-SVD method will be the technique of choice rather than SVD or first moment method.