Yoshito Tsushima

Metformin is widely used to treat diabetes, but induces changes in glucose uptake in both normal organs and tumors. Here, we review the effects of metformin on the uptake of 1 8F-fludeoxyglucose (18F-FDG) in tissues and tumors, and its influence on 18F-FDG positron emission tomographic imaging (18F-FDG PET), as well as the mechanisms involved. This is an important issue, because metformin has diverse effects on tissue uptake of 18F-FDG, and this can affect the quality and interpretation of PET images. Metformin increases glucose uptake in the gastrointestinal tract, cerebral white matter, and the kidney, while regions of the cerebrum associated with memory show decreased glucose uptake, and the myocardium shows no change. Hepatocellular carcinoma and breast cancer show increased glucose uptake after metformin administration, while thyroid cancer shows decreased uptake, and colon and pancreatic cancers show no change. A high-energy diet increases 18F-FDG uptake, but this effect is blocked by metformin. Withdrawal of metformin 48 h before PET image acquisition is widely recommended. However, based on our review of the literature, we propose that the differentiation of metformin discontinuation could be reasonable. But future clinical trials are still needed to support our viewpoint.

Purpose: Proprioceptive feedback is crucial for motor control and stabilization of the shoulder joint in everyday life and sports. Shoulder dislocation causes anatomical and proprioceptive feedback damage that contributes to subsequent dislocations. Previous recurrent anterior shoulder instability (RSI) studies did not investigate functional neuroplasticity related to proprioception of the injured shoulder. Thus, we aimed to study the differences in neuroplasticity related to motor control between patients with RSI and healthy individuals, using functional magnetic resonance imaging, and assess the effects of peripheral proprioceptive deficits due to RSI on CNS activity. Methods: Using passive shoulder motion and voluntary shoulder muscles contraction tasks, we compared the CNS correlates of proprioceptive activity between patients having RSI (n = 13) and healthy controls (n = 12) to clarify RSI pathophysiology and the effects of RSI-related peripheral proprioceptive deficits on CNS activity. Results: Decreased proprioception-related brain activity indicated a deficient passive proprioception in patients with RSI (P < 0.05 family-wise error, cluster level). Proprioceptive afferent-related right cerebellar activity significantly negatively correlated with the extent of shoulder damage (P = 0.001, r = −0.79). Functional magnetic resonance imaging demonstrated abnormal motor control in the CNS during voluntary shoulder muscles contraction. Conclusion: Our integrated analysis of peripheral anatomical information and brain activity during motion tasks can be used to investigate other orthopedic diseases.

Objectives: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD). In the present study, we evaluated the inflammatory activity of the ascending aorta in RA patients who received biological treatment. Methods: We assessed the aortic wall inflammation of RA patients using ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography before and after 6 months of biologic therapies. We also compared the inflammatory activity at the aortic wall in RA patients with remission or low disease activity (RLDA) and those with moderate or high disease activity (MHDA). The aortic uptake was measured by the standardized uptake value (SUV) and the target-to-background ratio (TBR). Results: A total of 64 patients were included in the analysis (mean age, 58.4 ± 13.8 years old; female, 77%). The Disease Activity Score for 28 joints (DAS28) erythrocyte sedimentation rate (ESR) had significantly decreased after 6 months: from 5.0 ± 1.2 to 3.3 ± 1.2 (p < 0.001). The FDG uptake in the ascending aorta changed from baseline to 6 months, showing a maximum SUV (SUV_max) of 1.83 ± 0.34 to 1.90 ± 0.34 (p = 0.059) and TBR of 1.71 ± 0.23 to 1.75 ± 0.24 (p = 0.222). The SUV_max and TBR after 6 months were significantly higher in the RLDA group than in the MHDA group (2.05 ± 0.32 vs. 1.79 ± 0.33 (p = 0.002) and 1.89 ± 0.33 vs. 1.65 ± 0.20 (p = 0.001), respectively). The percentage of monocytes also significantly increased from baseline to 6 months: from 5.9 ± 1.6 to 6.9 ± 2.6 (p = 0.032). Conclusion: The inflammation activity at the ascending aorta in RA patients did not change significantly after 6 months of biological treatment. RA patients with a low disease activity or in clinical remission after 6 months of biological treatment still had an increased inflammatory activity at the aortic wall.

Background: Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and the treatment response to biologics in RA patients using FDG-PET/CT. Methods: Sixty RA patients (male, n = 14; female, n = 46; average age, 58.3 years) treated with biologic agents were included in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The maximum standardized uptake value (SUVmax) was used as a representative value for the assessment of the FDG uptake in periodontal tissue and joints including the bilateral shoulders, elbows, wrists, hip, knees, and ankle joints. The Disease Activity Score (DAS) 28-CRP and the following clinical parameters were assessed: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and matrix metalloproteinase 3 (MMP-3). The relationship between the treatment response of RA and the baseline SUVmax of the periodontal tissue was evaluated. Results: The baseline periodontal SUVmax was related to patient age (r = 0.302, p = 0.009) and the ACPA level (r = 0.265, p = 0.025). The DAS28-CRP, CRP, ESR, MMP-3, and joint SUVmax values were significantly decreased after 6 months of biological therapy. However, the mean periodontal SUVmax, ACPA, and RF showed no significant changes after treatment. There was a significantly negative correlation between the baseline periodontal SUVmax and the treatment response of DAS28-CRP (r = − 0.369, p = 0.004). Conclusion: There was a negative correlation between the extent of PD at baseline and the treatment response of RA patients who received biological therapy. The evaluation of the periodontal condition is considered to be an essential part for the management of RA.

Objective:To assess the incidence and types of sensation of smell and taste during intravenous injection of five kinds of contrast media (CM) in computed tomography (CT) examinations.Methods:735 patients who underwent contrast enhanced (CE)-CT between 14 March 2016 and 5 April 2016 were enrolled. Medical staff asked patients whether they felt heat sensation and sensation of smell and taste during intravenous injection of CM (one of the following: Iopromide, Iomeprol, Iopamidol, Iohexol and Ioversol) after their CE-CT. If the patients stated having felt the sensation of smell or taste, they were also asked what kind of smell or taste. Next, 30 ml of each CM were poured into high purity pet cups for radiological technologists to smell directly. Radiological technologists were asked whether or not each CM had any smell.Results:The sensation of smell and taste incidence for Iopromide were 24.3% and 18.9%, respectively, which were significantly higher than those for other CM (p <0.05). The highest incidence of...

Objectives:To investigate the distribution and clearance of retained gadolinium (Gd) in various parts of the brain after intravenously administering a Gd-based contrast agent (GBCA) in normal and renal failure mouse models.Materials and Methods:Two different mouse models: normal (n = 12) and renal failure (n = 12) were used. Clinical GBCAs (Gd-DTPA-BMA, 5 mmol/kg or Gd-DOTA, 5 mmol/kg) were intravenously administered five times per week for 4 weeks. Both groups were divided into two subgroups based on the time-point for sample collection: 3 days (3d) and 45 days (45d) after the last injection. Normal saline (5 mL/kg) was intravenously administered to mice of the control groups in the same manner. Samples of the following parts of the mouse brain were obtained on dissection: olfactory bulb, cerebral cortex, hippocampus, thalamus, midbrain, cerebellum, pons and medulla. 158Gd concentrations in each sample were quantified using inductively coupled plasma mass spectrometry.Results:The olfactory bulb had the h...

We aimed to assess the usefulness of positron emission tomography (PET) using the amino acid tracer L-3-[18F] fluoro-alpha-methyl tyrosine (FAMT) in detecting metastatic liver lesions compared with 2-[18F]-fluoro-2-deoxyglucose (FDG). We included 24 patients with liver metastases who underwent both FDG-PET/computed tomography (CT) and FAMT-PET/CT. Maximum standardized uptake value (SUVmax) and tumor-to-liver parenchymal (T/L) ratio were analyzed to evaluate the correlation between FDG and FAMT uptakes in metastatic liver lesions; adenocarcinoma (AC, n = 21), squamous cell carcinoma (SCC, n = 23), neuroendocrine tumor (NET, n = 9), and carcinoid tumor (CAR, n = 6). We detected 59 lesions on performing either FDG-PET or FAMT-PET. NETs had significantly lower T/L ratios for FAMT (median, 1.00; range, 0.86–1.34) compared with those for FDG (median 2.86; range 1.70–6.13, p < 0.01). CAR tumors tended to reveal lower T/L ratios for FDG (median 1.10; range 0.78–1.92) than those for FAMT (median 1.80; range 0.80–2.34). Comparison of T/L ratios of SCC and AC revealed that FAMT in the metastatic liver lesions of SCC was higher than those of AC (p < 0.05). FAMT-PET could detect metastatic liver lesions from various cancers, except NET.

Purpose To help establish consensus on the safe use of contrast media in Japan. Materials and methods Questionnaires were sent to accredited teaching hospitals with radiology residency programs. Results The reply rate was 45.4 % (329/724). For contrast-induced nephropathy (CIN), chronic and acute kidney diseases were considered a risk factor in 96.7 and 93.6 %, respectively, and dehydration in 73.9 %. As preventive actions, intravenous hydration (89.1 %) and reduction of iodinated contrast media dose (86.9 %) were commonly performed. For nephrogenic systemic fibrosis (NSF), chronic and acute kidney diseases were considered risk factors in 98.5 and 90.6 %, respectively, but use of unstable gadolinium-based contrast media was considered a risk factor in only 55.6 %. A renal function test was always (63.5 % in iodinated; 65.7 % in gadolinium) or almost always (23.1; 19.8 %) performed, and estimated glomerular filtration rate (eGFR) was the parameter most frequently used (80.8; 82.6 %). For the patients with risk factors for acute adverse reaction (AAR), steroid premedication or/and change of contrast medium were frequent preventive actions, but intravenous steroid administration immediately before contrast media use was still performed. Conclusion Our questionnaire survey revealed that preventive actions against CIN were properly performed based on patientsʼ eGFR. Preventive actions against NSF and AAR still lacked consensus.

Background: Previous clinical studies have revealed the potential of [¹⁸F]-fluoro-L-α-methyltyrosine (¹⁸F-FAMT) for the differential diagnosis of malignant tumours from sarcoidosis. However, one concern regarding the differential diagnosis with ¹⁸F-FAMT is the possibility of false negatives given the small absolute uptake of ¹⁸F-FAMT that has been observed in some malignant tumours. The aim of this study was to evaluate a usefulness of dynamic ¹⁸F-FAMT positron emission tomography (PET) for differentiating malignant tumours from granulomas. Methods: Rats bearing both granulomas (Mycobacterium bovis bacillus Calmette-Guérin (BCG)-induced) and tumours (C6 glioma cell-induced) underwent dynamic 2-deoxy-2-[¹⁸F]-fluoro-D-glucose (¹⁸F-FDG) PET and ¹⁸F-FAMT PET for 120 min on consecutive days. Time-activity curves, static images, mean standardized uptake values (SUVs) and the SUV ratios (SUVRs; calculated by dividing SUV at each time point by that of 2 min after injection) were assessed. Results: In tumours, ¹⁸F-FAMT showed a shoulder peak immediately after the initial distribution followed by gradual clearance compared with granulomas. Although the mean SUV in the tumours (1.00 ± 0.10) was significantly higher than that in the granulomas (0.88 ± 0.12), a large overlap was observed. In contrast, the SUVR was markedly higher in tumours than in granulomas (50 min/2 min, 0.72 ± 0.06 and 0.56 ± 0.05, respectively) with no overlap. The dynamic patterns, SUVR, and mean SUV of ¹⁸F-FDG in the granulomas were comparable to those in the tumours. Conclusions: Dynamic ¹⁸F-FAMT and SUVR analysis might compensate for the current limitations and help in improving the diagnostic accuracy of ¹⁸F-FAMT.

Positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) can detect the presence of synovitis in rheumatoid arthritis (RA) patients. The aim of this study was to investigate whether the findings of FDG-PET matched the conventional assessments of the disease activity score (DAS) 28, DAS28-CRP, simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in RA patients receiving tocilizumab (TCZ) therapy. Seventeen RA patients treated with TCZ were assessed. FDG-PET was performed at baseline and three and six months after the initiation of TCZ therapy. The maximum SUV (SUVmax) of the bilateral shoulder, elbow, wrist, hip, knee and ankle joints were added together (total SUV) and were used to assess the degree of FDG uptake as a representative parameter. The correlations between the ΔSUV and the difference in the clinical parameters at baseline and at each observation period, and the differences in each clinical parameters, were assessed. The ΔSUV, the differences in the total SUV at baseline and at three/six months after starting treatment positively correlated with the ΔDAS28 (r = 0.615 p = 0.009/ r = 0.775 p < 0.001), ΔDAS28-CRP (r = 0.696, p = 0.002/ r = 0.828, p < 0.001), ΔSDAI (r = 0.652, p = 0.005/ r = 0.686, p = 0.002) and ΔCDAI (r = 0.662, p = 0.004/ r = 0.711, p = 0.001) for each period. The total SUV was significantly decreased at three and six months after the initiation of TCZ (p < 0.05). A reduction in the FDG uptake was observed at three and six months after the initiation of TCZ therapy. The disease activity estimated on FDG-PET/CT matched the conventional parameters following the TCZ therapy in RA patients.