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The brain's energy budget can be non-invasively assessed with different imaging modalities such as functional MRI (fMRI) and PET (fPET), which are sensitive to oxygen and glucose demands, respectively. The introduction of hybrid PET/MRI systems further enables the simultaneous acquisition of these parameters. Although a recently developed method offers the quantification of task-specific changes in glucose metabolism (CMRGlu) in a single measurement, direct comparison of the two imaging modalities is still difficult because of the different temporal resolutions. Thus, we optimized the protocol and systematically assessed shortened task durations of fPET to approach that of fMRI. Twenty healthy subjects (9 male) underwent one measurement on a hybrid PET/MRI scanner. During the scan, tasks were completed in four blocks for fMRI (4 × 30 s blocks) and fPET: participants tapped the fingers of their right hand repeatedly to the thumb while watching videos of landscapes. For fPET, subjects were randomly assigned to groups of n = 5 with varying task durations of 10, 5, 2 and 1 min, where task durations were kept constant within a measurement. The radiolabeled glucose analogue [18F]FDG was administered as 20% bolus plus constant infusion. The bolus increases the signal-to-noise ratio and leaves sufficient activity to detect task-related effects but poses additional challenges due to a discontinuity in the tracer uptake. First, three approaches to remove task effects from the baseline term were evaluated: (1) multimodal, based on the individual fMRI analysis, (2) atlas-based by removing presumably activated regions and (3) model-based by fitting the baseline with exponential functions. Second, we investigated the need to capture the arterial input function peak with automatic blood sampling for the quantification of CMRGlu. We finally compared the task-specific activation obtained from fPET and fMRI qualitatively and statistically. CMRGlu quantified only with manual arterial samples showed a strong correlation to that obtained with automatic sampling (r = 0.9996). The multimodal baseline definition was superior to the other tested approaches in terms of residuals (p < 0.001). Significant task-specific changes in CMRGlu were found in the primary visual and motor cortices (tM1 = 18.7 and tV1 = 18.3). Significant changes of fMRI activation were found in the same areas (tM1 = 16.0 and tV1 = 17.6) but additionally in the supplementary motor area, ipsilateral motor cortex and secondary visual cortex. Post-hoc t-tests showed strongest effects for task durations of 5 and 2 min (all p < 0.05 FWE corrected), whereas 1 min exhibited pronounced unspecific activation. Percent signal change (PSC) was higher for CMRGlu (∼18%–27%) compared to fMRI (∼2%). No significant association between PSC of task-specific CMRGlu and fMRI was found (r = 0.26). Using a bolus plus constant infusion protocol, the necessary task duration for reliable quantification of task-specific CMRGlu could be reduced to 5 and 2 min, therefore, approaching that of fMRI. Important for valid quantification is a correct baseline definition, which was ideal when task-relevant voxels were determined with fMRI. The absence of a correlation and the different activation pattern between fPET and fMRI suggest that glucose metabolism and oxygen demand capture complementary aspects of energy demands. •Quantification of task-specific CMRGlu with 20% bolus plus constant infusion.•Functional PET task durations down to 1 min were evaluated.•Active primary regions overlap between BOLD and CMRGlu.•No significant correlation between BOLD and CMRGlu.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer’s disease. Here we report on six patients with mild to moderate Alzheimer’s disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer’s Disease Assessment Scale—cognitive subscale as the primary outcome measure. Electroencephalography and [ 18 F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

Purpose Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12 months after Achilles tendon rupture as measured using PET and power Doppler ultrasonography (PDUS). Methods The study group comprised 23 patients with surgically repaired Achilles tendon rupture who were investigated at 3 months ( n  = 7), 6 months ( n  = 7) and 12 months ( n  = 9) after surgery. The triceps surae complex was loaded over 20 min of slow treadmill walking while a radioactive tracer ( 18 F-FDG) was administered prior to PET. Vascularization was measured in terms of PDUS flow activity, and patient-reported outcomes were scored using the Achilles tendon rupture score (ATRS) and sports assessment (VISA-A) questionnaire. Results Relative glucose uptake ( 18 F-FDG) was higher in repaired tendons than in intact tendons at all time-points (6, 3 and 1.6 times higher at 3, 6 and 12 months, respectively; P  ≤ 0.001), and was also higher in the tendon core than in the periphery at 3 and 6 months ( P  ≤ 0.02), but lower at 12 months ( P  = 0.06). Relative glucose uptake was negatively related to ATRS at 6 months after repair ( r  = −0.89, P  ≤ 0.01). PDUS flow activity was higher in repaired tendons than in intact tendons at 3 and 6 months ( P  < 0.05 for both), but had normalized by 12 months. Conclusion These data demonstrate that the healing process as determined by metabolic activity and vascularization continues for 6 months after injury when large loads are typically allowed on the tendon. Indeed, metabolic activity remained elevated for more than 1 year after injury despite normalized vascularization. The robust negative correlation between tendon metabolism and patient-reported outcome suggests that a high metabolic activity 6 months after the injury may be related to a poor clinical healing outcome.

Purpose To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT). Methods This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan–Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS. Results Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ≤32 mL had worse median OS (14.8 vs. 29.7 months, p  < 0.001). As a continuous variable, higher tMTV-pre (per 10-mL increase) remained associated with worse OS (HR = 1.03, p  < 0.001) after controlling for other variables. A significant interaction between radiation dose and tMTV-pre occurred for OS ( p  = 0.002), demonstrating that the negative prognostic impact of tMTV-pre decreased as radiotherapy dose increased. Among patients with tMTV-pre ≤32 mL, there was no difference in survival according to radiotherapy dose delivered ( p  = 0.694). However, median OS was inferior in patients with tMTV-pre >32 mL who received ≤60 Gy compared with those who received 61–69 Gy or ≥70 Gy ( p  = 0.001). Conclusions Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.

Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and ¹⁸FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6%±10) whereas males tended to increase it (+5.5%±18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from \"control networks\" (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

Background18F-fluorodeoxyglucose (FDG) has been useful in the evaluation of myocardial inflammatory processes. However, it is challenging to identify them due to physiological 18F-FDG uptake. There are no publications demonstrating the application of FDG in post-transplant rejection in humans yet. The aim of this study is to determine the feasibility of suppression of myocardial FDG uptake in post-transplant patients, comparing three different protocols of preparation.MethodsTen patients after heart transplantation were imaged by FDG associated with three endomyocardial biopsies (EMB), scheduled in the first year after the procedure. Before each imaging, patients were randomized to one of three preparations: (1) hyperlipidic-hypoglycemic diet; (2) fasting longer than 12 hours; and (3) fasting associated with intravenous heparin. All patients would undergo the three methods. FDG images were analyzed using visual analysis scores and relative radiotracer cardiac uptake (RRCU).ResultsThe suppression rate of radiotracer activity ranged from 55% to 62%. Visual analysis showed that preparation 3 presented less efficacy in the suppression compared to the others. However, RRCU did not show difference between the preparations.ConclusionsSuppression of physiological myocardial FDG uptake after cardiac transplantation is feasible. The usefulness of heparin in the suppression is unclear.

Introduction The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient’s unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine. Methods This substudy was performed within the framework of a wider prospective multicenter study on the predictive value of early FDG PET-CT response assessment (SoMore study). A lesion-based response analysis was performed, including all measurable lesions identified on the baseline PET. On a per-patient basis, a descriptive 4-class response categorization was applied based upon the presence and proportion of non-responding lesions. For dichotomic response comparison, all patients with at least one resistant lesion were classified as non-responding. Results On baseline FDG PET-CT, 124 measurable “target” lesions were identified in 38 patients. Early mR assessments showed 18 patients (47 %) without treatment resistant lesions and 12 patients (32 %) with interlesional response heterogeneity. The NPV and PPV of early mR were 85 % (35/41) and 84 % (70/83), respectively, on a per-lesion basis and 95 % (19/20) and 72 % (13/18), respectively, on a dichotomized per-patient basis. Conclusions Early mR assessment performed after one cycle of sorafenib-capecitabine in mCRC is highly predictive of non-response at a standard response assessment time. The high NPV (95 %) of early mR could be useful as the basis for early treatment discontinuation or adaptation to spare patients from exposure to non-effective drugs.

HIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as a pathophysiological explanation. We compared the uptake of (18)F-fluorodeoxyglucose (FDG) by PET in four arterial regions, and factors associated with FDG uptake in well-treated HIV-infected patients without cardiovascular disease (CVD) and healthy controls. We prospectively scanned 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers with FDG PET/CT, measuring standardized uptake values (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. We performed correlation analyses between FDG uptake and intima-media thickness (IMT), and soluble biomarkers of inflammation. We found no difference in arterial FDG uptake between the HIV-infected patients and healthy controls quantified either as mean SUVmax or target-to background ratio in the carotid region, the ascending aorta, the descending aorta, or the abdominal aorta. Correlations between SUV, IMT, and soluble biomarkers were scarce in both groups. In a group of optimally treated HIV-infected patients with full viral suppression, low Framingham risk score and no known CVD, we found no evidence of increased arterial inflammation as assessed by FDG PET/CT compared to healthy volunteers.

Recent in vitro studies suggest that lactate, rather than glucose, may be the preferred fuel for neuronal metabolism. The authors examined the effect of lactate on global brain glucose uptake in euglycemic human subjects using 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight healthy men, aged 40 to 54 years, underwent a 60-minute FDG-PET scan on two occasions in random order. On one occasion, 6.72% sodium lactate was infused at a rate of 50 μmol · kg−1 · min−1 for 20 minutes and then reduced to 30 μmol · kg−1 · min−1; 1.4% sodium bicarbonate was infused as a control on the other occasion. Plasma glucose levels were not different between the two groups (5.3 ± 0.23 and 5.3 ± 0.24 mmol/L, P = 0.55). Plasma lactate was significantly elevated by lactate infusion (4.08 ± 0.35 vs. 0.63 ± 0.22 mmol/L, P < 0.0005. The whole-brain rate of glucose uptake was significantly reduced by approximately 17% during lactate infusion (0.195 ± 0.022 vs. 0.234 ± 0.020 μmol · g−1 · min−1, P = 0.001). The authors conclude that, in vivo in humans, circulating lactate is used by the brain at euglycemia, with sparing of glucose.

F-18 fluorodeoxyglucose ( 18F-FDG) positron emission tomography (PET) is a useful tool for the detection of local inflamed atherosclerotic lesions. This study used hybrid PET/computed tomography (CT) to examine the effects of 2 doses of atorvastatin on 18F-FDG uptake in atherosclerotic plaques in Japanese adults with stable angina pectoris who were scheduled to undergo percutaneous coronary intervention (PCI). This was a prospective, randomized, investigator-blinded, open-label study in patients with dyslipidemia (total cholesterol ≥220 mg/dL and/or LDL-C ≥140 mg/dL) who were scheduled to undergo PCI for stable angina pectoris and had not received any lipid-lowering drugs within 1 year before enrollment. Patients were randomly allocated to receive atorvastatin 5 or 20 mg/d for 6 months. At baseline (the day after PCI), 18F-FDG uptake in the ascending aorta and femoral artery was determined using PET/CT imaging, and the mean target-to-background ratio (TBR) was calculated in individual plaques. The same regions were assessed by PET/CT after 6 months of treatment. Changes from baseline to follow-up in the lipid profile, serum malondialdehyde-modified LDL-C (MDA–LDL-C), and serum high-sensitivity C-reactive protein (hs-CRP) were also examined. Drug adherence, adverse events, and changes in medications were monitored at monthly outpatient visits. Of 32 patients initially screened, 2 were excluded due to newly diagnosed cancer; thus, 30 patients were randomly assigned to treatment, 15 in each group. Patients were predominantly male (18 [60%]), with a mean (SD) age of 54 (11) years, mean body weight of 65 (12) kg, and mean total cholesterol, HDL-C, and triglyceride concentrations of 240 (29), 48 (14), and 180 (102) mg/dL, respectively. After 6 months, the 20-mg group had significant reductions from baseline in mean (SD) TBR in the ascending aorta (from 1.15 [0.14] to 1.05 [0.12]; percent change, −7.9% [9.4%]; P = 0.007) and the femoral artery (from 1.12 [0.11] to 1.02 [0.11]; percent change, −9.9% [13.8%]; P = 0.012). The corresponding changes from baseline were not statistically significant in the 5-mg group. The differences in percent change in TBR in the 2 locations were not significant between groups. When data from the 2 groups were combined, the overall reduction in TBR from baseline to 6 months was significant in both the ascending aorta ( P = 0.003) and the femoral artery ( P = 0.021). The decreases in TBR in both arteries were significantly correlated with reductions in LDL-C (ascending aorta: r 2 = 0.230 [ P = 0.012]; femoral artery: r 2 = 0.338 [ P = 0.003]), MDA–LDL-C (ascending aorta: r 2 = 0.183 [ P = 0.028]; femoral artery: r 2 = 0.247 [ P = 0.010]), and hs-CRP (ascending aorta: r 2 = 0.132 [ P = 0.048]; femoral artery: r 2 = 0.271 [ P = 0.007]). One patient in the 5-mg group and 2 patients in the 20-mg group had ∼2-fold increases in serum aminotransferases on a single occasion; however, no specific musculoskeletal or hepatic adverse events were observed, and aminotransferase values decreased to within normal ranges without changes in the atorvastatin dose. Six months of treatment with atorvastatin 20 mg, but not 5 mg, was associated with a significant reduction in TBR in the ascending aorta and femoral artery in these Japanese adults with dyslipidemia undergoing PCI for stable angina pectoris. University Hospital Medical Information Network Clinical Trials Registry identifier: C000000371.