Alzheimer's Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?

The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.

"Visualization" of pain using cerebral 18F-FDG PET/CT following surgical treatment of lumbar disc herniation.

PURPOSE: We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus. METHODS: Patients scheduled for surgery due to LDH underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography less than two weeks prior to surgery. Their thalamic FDG uptake was measured and expressed as the mean and partial volume corrected mean standardized uptake values (SUVmean and cSUVmean). These measures were compared with patient-related outcome measures collected pre- and 1-year post-operatively: back and leg pain on a 0-100 VAS scale and health-related quality of life as measured by the EuroQol-5D (EQ-5D). RESULTS: Twenty-six patients (ten females) aged 49.7 ± 7.4 (mean ± SD) years were included. There was a significant correlation between painful body side and increased contralateral thalamic uptake of FDG, with regard to cSUVmean values. Correlation analyses including clinical parameters and cSUVmean indicated some association with 1-year change in EQ-5D. CONCLUSION: These preliminary data sustain the hypothesis that unilateral pain in patients with LDH is associated with increased glucose metabolism in the contralateral thalamus, suggesting a central role of thalamus in chronic pain perception.

"Global" cardiac atherosclerotic burden assessed by artificial intelligence-based versus manual segmentation in 18F-sodium fluoride PET/CT scans: Head-to-head comparison.

BACKGROUND: Artificial intelligence (AI) is known to provide effective means to accelerate and facilitate clinical and research processes. So in this study it was aimed to compare a AI-based method for cardiac segmentation in positron emission tomography/computed tomography (PET/CT) scans with manual segmentation to assess global cardiac atherosclerosis burden. METHODS: A trained convolutional neural network (CNN) was used for cardiac segmentation in 18F-sodium fluoride PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients and compared with manual segmentation. Parameters for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, SUVtotal) were analyzed by Bland-Altman Limits of Agreement. Repeatability with AI-based assessment of the same scans is 100%. Repeatability (same conditions, same operator) and reproducibility (same conditions, two different operators) of manual segmentation was examined by re-segmentation in 25 randomly selected scans. RESULTS: Mean (± SD) values with manual vs. CNN-based segmentation were Vol 617.65 ± 154.99 mL vs 625.26 ± 153.55 mL (P = .21), SUVmean 0.69 ± 0.15 vs 0.69 ± 0.15 (P = .26), SUVmax 2.68 ± 0.86 vs 2.77 ± 1.05 (P = .34), and SUVtotal 425.51 ± 138.93 vs 427.91 ± 132.68 (P = .62). Limits of agreement were - 89.42 to 74.2, - 0.02 to 0.02, - 1.52 to 1.32, and - 68.02 to 63.21, respectively. Manual segmentation lasted typically 30 minutes vs about one minute with the CNN-based approach. The maximal deviation at manual re-segmentation was for the four parameters 0% to 0.5% with the same and 0% to 1% with different operators. CONCLUSION: The CNN-based method was faster and provided values for Vol, SUVmean, SUVmax, and SUVtotal comparable to the manually obtained ones. This AI-based segmentation approach appears to offer a more reproducible and much faster substitute for slow and cumbersome manual segmentation of the heart.

Molecular imaging in management of colorectal metastases by the interventional oncologist.

Interventional oncologists provide several effective treatment options for patients with metastatic colorectal cancer (mCRC), including embolization and ablation-based techniques. Molecular imaging methods such as positron emission tomography (PET) can play an important role in managing mCRC patients. In this review, we aim to highlight the role of molecular imaging in mCRC management by interventional oncologists including: initial staging and pretreatment planning; predicting molecular subtypes, prognosis, and treatment outcomes; intraprocedural guidance; and assessing treatment response and post-procedural monitoring.

Atherosclerosis Burdens in Diabetes Mellitus: Assessment by PET Imaging.

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.

A critical review of radiotracers in the positron emission tomography imaging of traumatic brain injury: FDG, tau, and amyloid imaging in mild traumatic brain injury and chronic traumatic encephalopathy.

PURPOSE: Positron emission tomography (PET) has been widely utilized in the study of traumatic brain injury (TBI) for decades. While most applications of PET have attempted to assess neuronal function after TBI, more recently, novel radiotracers have sought to image biomarkers in the context of TBI and chronic traumatic encephalopathy (CTE). METHODS: This review will begin with an overview of TBI and CTE along with the acute and chronic pathophysiological consequences of TBI. Next, glycolysis, beta-amyloid, and tau protein radiotracers will be critically assessed in light of the most recent imaging studies available. CONCLUSIONS: Based on the scientific relevance of such radiotracers to the molecular processes of TBI and CTE along with the broader evidence of radiotracer specificity and selectivity, this review will weigh the strengths and weaknesses of each radiotracer. Nonetheless, the evidence indicates that PET will continue to be a powerful modality in the diagnosis of TBI-related conditions.

Quantitative thoracic aorta calcification assessment by 18F-NaF PET/CT and its correlation with atherosclerotic cardiovascular disorders and increasing age.

OBJECTIVES: We aimed to assess the correlation between age and cardiovascular risk factors with NaF-PET/CT imaging in the thoracic aorta (TA). METHODS: In this prospective study, 80 healthy controls and 44 patients with chest pain underwent NaF-PET/CT imaging, and three segments of the aorta (ascending, arch, and descending) were examined. Average SUVmax, SUVmean, and Alavi-Carlsen Score (ACS) were calculated in each segment and the entire vessel. The degree of NaF uptake in controls and patients and its correlation with age were determined. Multivariate linear regression and logistic regression models were employed to determine the predictabilities of Framingham Risk Score (FRS) and unfavorable cardiovascular disease (CVD) risk profile by these measurements. RESULTS: Average SUVmax, average SUVmean, and ACS were significantly higher in patients than in controls, and all correlated well with age. The correlation of average SUVmean with age was significant in both controls (r = 0.32, p = 0.04) and patients (r = 0.64, p < 0.001). ACS of the entire TA was a stronger predictor of FRS compared with average SUVmax and average SUVmean (adjusted R2 = 0.38, standardized ß = 0.58, p < 0.001). ACS was a significant predictor of unfavorable CVD risk profile as compared with other values (odds ratio = 1.006, 95% CI = 1.000-1.013, p = 0.05). CONCLUSIONS: Active calcification in TA correlates with age, and its correlation is higher among subjects with CVD risk factors. Global assessment (ACS) can predict unfavorable CVD risk profile. These data provide evidence for the potential role of NaF in assessing micro-calcification in arteries and its relations to cardiovascular events. KEY POINTS: • Global micro-calcification in the thoracic aorta as measured by NaF-PET/CT imaging correlates with increasing age. • The extent of the correlation was higher among patients with cardiovascular disease (CVD) risk factors. • These data provide evidence for the potential role of NaF in assessing active calcification in arteries and its relations to cardiovascular events.

Carotid artery molecular calcification assessed by [18F]fluoride PET/CT: correlation with cardiovascular and thromboembolic risk factors.

OBJECTIVES: There is growing evidence that sodium fluoride ([18F]fluoride) PET/CT can detect active arterial calcifications at the molecular stage. We investigated the relationship between arterial mineralization in the left common carotid artery (LCC) assessed by [18F]fluoride PET/CT and cardiovascular/thromboembolic risk. METHODS: In total, 128 subjects (mean age 48 ± 14 years, 51% males) were included. [18F]fluoride uptake in the LCC was quantitatively assessed by measuring the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice. Average SUVmax (aSUVmax) was calculated over all slices and correlated with 10-year risk of cardiovascular events estimated by the Framingham model, CHA2DS2-VASc score, and level of physical activity (LPA). RESULTS: The aSUVmax was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA, p < 0.01) and thromboembolic (one-way ANOVA, p < 0.01) events, and it was significantly lower in patients with greater LPA (one-way ANOVA, p = 0.02). On multivariable linear regression analysis, age ( = 0.07, 95% CI 0.05 - 0.10, p < 0.01), body mass index ( = 0.02, 95% CI 0.01 - 0.03, p < 0.01), arterial hypertension ( = 0.15, 95% CI 0.08 - 0.23, p < 0.01), and LPA ( = -0.10, 95% CI -0.19 to -0.02, p=0.02) were independent associations of aSUVmax. CONCLUSIONS: Carotid [18F]fluoride uptake is significantly increased in patients with unfavorable cardiovascular and thromboembolic risk profiles. [18F]fluoride PET/CT could become a valuable tool to estimate subjects' risk of future cardiovascular events although still major trials are needed to further evaluate the associations found in this study and their potential clinical usefulness. KEY POINTS: • Sodium fluoride ([18F]fluoride) PET/CT imaging identifies patients with early-stage atherosclerosis. • Carotid [18F]fluoride uptake is significantly higher in patients with increased risk of cardiovascular and thromboembolic events and inversely correlated with the level of physical activity. • Early detection of arterial mineralization at a molecular level could help guide clinical decisions in the context of cardiovascular risk assessment.

Assessment of atherosclerosis in multiple myeloma and smoldering myeloma patients using 18F- sodium fluoride PET/CT.

BACKGROUND: To compare the NaF uptake in the thoracic aorta and whole heart, as an early indicator of atherosclerosis, in multiple myeloma (MM) and smoldering multiple myeloma (SMM) patients with a healthy control (HC) group. METHODS: Forty-four untreated myeloma patients (35 MM and nine SMM) and twenty-six age and gender-matched HC subjects were collected. Each individual's NaF uptake in three parts of the aorta (AA: ascending aorta, AR: aortic arch, DA: descending aorta) and the whole heart was segmented. Average global standardized uptake value means were derived by sum of the product of each slice area divided by the sum of those slice areas. Results were reported as target to background ratio (TBR). RESULTS: There was a significant difference between the NaF uptake in the thoracic aorta of myeloma and HC groups [AA (myeloma = 1.82 ± 0.21, HC = 1.24 ± 0.02), AR (myeloma = 1.71 ± 0.19, HC = 1.28 ± 0.03) and DA (myeloma = 1.96 ± 0.28, HC = 1.38 ± 0.03); P-values < 0.001]. The difference in the whole heart NaF uptake between two groups was also significant (P < 0.001). CONCLUSIONS: We observed a higher uptake of NaF in the thoracic aorta and whole heart of myeloma patients in comparison to the matched control group.

18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications.

In a healthy body, homeostatic actions of osteoclasts and osteoblasts maintain the integrity of the skeletal system. When cellular activities of osteoclasts and osteoblasts become abnormal, pathological bone conditions, such as osteoporosis, can occur. Traditional imaging modalities, such as radiographs, are insensitive to the early cellular changes that precede gross pathological findings, often leading to delayed disease diagnoses and suboptimal therapeutic strategies. 18F-sodium fluoride (18F-NaF)-positron emission tomography (PET) is an emerging imaging modality with the potential for early diagnosis and monitoring of bone diseases through the detection of subtle metabolic changes. Specifically, the dissociated 18F- is incorporated into hydroxyapatite, and its uptake reflects osteoblastic activity and bone perfusion, allowing for the quantification of bone turnover. While 18F-NaF-PET has traditionally been used to detect metastatic bone disease, recent literature corroborates the use of 18F-NaF-PET in benign osseous conditions as well. In this review, we discuss the cellular mechanisms of 18F-NaF-PET and examine recent findings on its clinical application in diverse metabolic, autoimmune, and osteogenic bone disorders.

Association of baseline subject characteristics with changes in coronary calcification assessed by 18F-sodium fluoride PET/CT.

OBJECTIVE: The goal of this study was to test if changes in coronary microcalcification over a two year period assessed by fluorine-18-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) are associated with baseline subject characteristics. SUBJECTS AND METHODS: This prospective study included healthy female (N=8, age 52±10 years, body mass index(BMI) 24±1.7kg/m2) and male (N=15, age 50±10 years, BMI 27±2.9kg/m2) participants who had 18F-NaF PET/CT scans taken two years apart. Imaging was performed 90 minutes after intravenous injection of 2.2MBq of 18F-NaF per kilogram of body weight. The analysis regions were selected on CT images by drawing volumes of interest around the entire heart using a semi-automatic segmentation method.Mean standardize uptake value (SUVmean) and maximum SUV (SUVmax) were calculated in the same regions of the registered PET images. Percent change in SUV between the two time points were correlated against baseline age, BMI, cardiovascular risk factors, and blood chemistry. RESULTS: In males, percent change in SUVmean over the two year period was positively correlated with baseline BMI (r=0.85, P<0.0001) and systolic blood pressure (r=0.65, P=0.0082). These baseline values were not significantly correlated with SUVmax in either gender. CONCLUSION: High BMI is a known risk factor for atherosclerosis. Our data showed that rate of increase in coronary microcalcification over time measured by 18F-NaF PET/CT is associated with baseline BMI and some clinical risk factors in males. Lack of such associations in females could be due to low sample size (N=8). Further prospective studies are needed to determine if baseline BMI and clinical factors could be used to predict rate of increase in coronary microcalcification which could provide the basis for managing the progression of atherosclerosis in patient-specific manner.

The Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Left-sided Endocarditis: Native vs Prosthetic Valves Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has emerged as a useful diagnostic tool for suspected infective endocarditis (IE) in patients with prosthetic valves or implantable devices. However, there is limited evidence regarding use of 18F-FDG-PET/CT for the diagnosis of native valve endocarditis (NVE). METHODS: Between 2014 and 2017, 303 episodes of left-sided suspected IE (188 prosthetic valves/ascending aortic prosthesis and 115 native valves) were studied. 18F-FDG-PET/CT accuracy was determined in the subgroups of patients with NVE and prosthetic valve endocarditis (PVE)/ascending aortic prosthesis infection (AAPI). Associations between inflammatory infiltrate patterns and 18F-FDG-PET/CT uptake were investigated in an exploratory ad hoc histological analysis. RESULTS: Among 188 patients with PVE/AAPI, the sensitivity, specificity, and positive and negative predictive values of 18F-FDG-PET/CT focal uptake were 93%, 90%, 89%, and 94%, respectively, while among 115 patients with NVE, the corresponding values were 22%, 100%, 100%, and 66%. The inclusion of abnormal 18F-FDG cardiac uptake as a major criterion at admission enabled a recategorization of 76% (47/62) of PVE/AAPI cases initially classified as "possible" to "definite" IE. In the histopathological analysis, a predominance of polymorphonuclear cell inflammatory infiltrate and a reduced extent of fibrosis were observed in the PVE group only. CONCLUSIONS: Use of 18F-FDG-PET/CT at the initial presentation of patients with suspected PVE increases the diagnostic capability of the modified Duke criteria. In patients who present with suspected NVE, the use of 18F-FDG-PET/CT is less accurate and could only be considered a complementary diagnostic tool for a specific population of patients with NVE.

Atherosclerosis imaging with 18F-sodium fluoride PET: state-of-the-art review.

PURPOSE: We examined the literature to elucidate the role of 18F-sodium fluoride (NaF)-PET in atherosclerosis. METHODS: Following a systematic search of PubMed/MEDLINE, Embase, and Cochrane Library included articles underwent subjective quality assessment with categories low, medium, and high. Of 2811 records, 1780 remained after removal of duplicates. Screening by title and abstract left 41 potentially eligible full-text articles, of which 8 (about the aortic valve (n = 1), PET/MRI feasibility (n = 1), aortic aneurysms (n = 1), or quantification methodology (n = 5)) were dismissed, leaving 33 published 2010-2012 (n = 6), 2013-2015 (n = 11), and 2016-2018 (n = 16) for analysis. RESULTS: They focused on coronary (n = 8), carotid (n = 7), and femoral arteries (n = 1), thoracic aorta (n = 1), and infrarenal aorta (n = 1). The remaining 15 studies examined more than one arterial segment. The literature was heterogeneous: few studies were designed to investigate atherosclerosis, 13 were retrospective, 9 applied both FDG and NaF as tracers, 24 NaF only. Subjective quality was low in one, medium in 13, and high in 19 studies. The literature indicates that NaF is a very specific tracer that mimics active arterial wall microcalcification, which is positively associated with cardiovascular risk. Arterial NaF uptake often presents before CT-calcification, tends to decrease with increasing density of CT-calcification, and appears, rather than FDG-avid foci, to progress to CT-calcification. It is mainly surface localized, increases with age with a wide scatter but without an obvious sex difference. NaF-avid microcalcification can occur in fatty streaks, but the degree of progression to CT-calcification is unknown. It remains unknown whether medical therapy influences microcalcification. The literature held no therapeutic or randomized controlled trials. CONCLUSION: The literature was heterogeneous and with few clear cut messages. NaF-PET is a new approach to detect and quantify microcalcification in early-stage atherosclerosis. NaF uptake correlates with cardiovascular risk factors and appears to be a good measure of the body's atherosclerotic burden, potentially suited also for assessment of anti-atherosclerotic therapy.

18F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification.

AIMS: To investigate the benefit of utilizing 18F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention. METHODS AND RESULTS: This retrospective study included 136 participants (ages 21-75, BMI 18-43 kg/m2): 86 healthy controls and 50 patients. CT heart segmentations were superimposed onto PET images and standard uptake values (SUV) were calculated by a semi-auto segmentation method of drawing volumes of interest around the heart. Intergroup comparisons were made matching 37 patient/control pairs based on age, gender, and BMI. ROC curves were generated to determine how well SUV and Framingham methods predicted patient status. Regressions including all 136 participants were performed between SUV, age, and BMI. Patients exhibited higher average SUV (SUVmean; P = 0.006) and Framingham scores (P = 0.02) than controls. However, ROC curves indicated that SUVmean could discriminate patients from controls (AUC = 0.63, P = 0.049), but Framingham scores could not (AUC = 0.44, P = 0.38). Calcium scores and maximum SUV (SUVmax) did not differ between patients and controls. SUVmean correlated with age and BMI among females (age, partial R2 = 0.16, P = 0.001; BMI, partial R2 = 0.12, P = 0.004) and males (age, partial R2 = 0.28, P < 0.0001; BMI, partial R2 = 0.22, P < 0.0001). CONCLUSION: Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUVmean, but were not sensitive enough to predict patient status. SUVmean values increased with age and BMI. Therefore, incorporation of NaF PET/CT into routine prognostic CAD assessment might prove beneficial for assessing early stage plaque calcification in coronary arteries. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01724749).

Comparison of 18F-sodium fluoride uptake in the whole bone, pelvis, and femoral neck of multiple myeloma patients before and after high-dose therapy and conventional-dose chemotherapy.

AIM: To compare the effects of high-dose therapy (HDT consisting of high-dose chemotherapy followed by autologous stem cell transplantation) and conventional-dose chemotherapy (non-HDT) on the uptake of 18F-sodium fluoride (NaF) in the whole bone, pelvis, and femoral neck of multiple myeloma (MM) patients. METHOD: The data of 19 MM patients who received HDT (61.5 (SD 5.6) years) and 11 MM patients who received conventional-dose chemotherapy (70.9 (SD 7.2) years) were collected in a prospective study. NaF PET/CT imaging was performed at baseline, and 8 weeks and 2 weeks after treatment for the HDT group and the non-HDT group, respectively. A CT-based algorithm was applied to segment the bones, and the global mean SUV (GSUVmean) of the whole bone and pelvis was calculated (OsiriX MD v.9.0, Pixmeo SARL; Bernex, Switzerland). In addition, regions of interest for the whole, medial, and lateral femoral neck were delineated bilaterally. Whole bone and pelvis measurements were replicated by two observers. RESULTS: The average GSUVmean in the whole bone and pelvis of the patients who underwent HDT significantly decreased from before to after treatment (- 16.27%, p = 0.02 and - 16.54%, p = 0.01, respectively). A significant decrease in the whole and lateral femoral neck was also observed bilaterally in the HDT group. No significant decrease in average GSUVmean was observed in the non-HDT group. A high level of inter-observer reliability was found in intra-class correlation (ICC for pre-treatment whole bone 0.983, post-treatment whole bone 0.989, pre-treatment whole pelvis 0.998, post-treatment whole pelvis 0.996). CONCLUSION: NaF uptake significantly decreased after treatment in patients who received high-dose therapy. A high level of agreement was observed between two operators for whole bone and pelvis measurements.

Incremental value of FDG-PET/CT to monitor treatment response in infectious spondylodiscitis.

OBJECTIVE: To assess the added value of serial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake analysis in predicting clinical response to treatment in infectious spondylodiscitis (IS). We sought to analyze changes in quantitative FDG-PET/CT parameters among patients with clinical response or treatment failure and to compare the sensitivity and specificity of serial FDG-PET/CT and MRI in predicting treatment response in IS. MATERIALS AND METHODS: This retrospective study consisted of 68 FDG-PET/CT examinations in 34 patients performed before and after at least 2 weeks of antibiotic treatment. Serial MRI scans were available in 32 (94%) patients before and after treatment. FDG-avid lesions were quantified as maximum standardized uptake value (SUVmax), partial-volume corrected lesion metabolic volume (LMV), and partial-volume corrected lesion metabolic activity (LMA). RESULTS: All FDG-PET/CT parameters significantly decreased in patients with clinical improvement (31/34, 91%, P < 0.001), while patients with disease progression did not show FDG-PET/CT improvement. FDG uptake decrease was similar between patients undergoing early assessment (< 6 weeks) compared with those performing FDG-PET/CT after 6 weeks of treatment. SUVmax, LMV, and LMA decrease over time was 39.0%, 97.4%, and 97.1%, respectively. In predicting clinical responses, SUVmax reduction > 15% and > 25% showed 94% and 89% sensitivity and 67% and 100% specificity compared with 37% and 50% of MRI, respectively. Low degree of agreement with clinical response was shown for MRI compared with FDG-PET/CT parameters using the Cohen kappa coefficient. CONCLUSIONS: FDG-PET/CT monitoring is a valuable tool to predict clinical response to treatment in IS and has greater sensitivity and specificity compared with MRI.

A prospective study of the feasibility of FDG-PET/CT imaging to quantify radiation-induced lung inflammation in locally advanced non-small cell lung cancer patients receiving proton or photon radiotherapy.

PURPOSE: This prospective study assessed the feasibility of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) to quantify radiation-induced lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT), and compared the differences in inflammation in the ipsilateral and contralateral lungs following proton and photon RT. METHODS: Thirty-nine consecutive patients with NSCLC underwent FDG-PET/CT imaging before and after RT on a prospective study. A novel quantitative approach utilized regions of interest placed around the anatomical boundaries of the lung parenchyma and provided lung mean standardized uptake value (SUVmean), global lung glycolysis (GLG), global lung parenchymal glycolysis (GLPG) and total lung volume (LV). To quantify primary tumor metabolic response to RT, an adaptive contrast-oriented thresholding algorithm was applied to measure metabolically active tumor volume (MTV), tumor uncorrected SUVmean, tumor partial volume corrected SUVmean (tumor-PVC-SUVmean), and total lesion glycolysis (TLG). Parameters of FDG-PET/CT scans before and after RT were compared using two-tailed paired t-tests. RESULTS: All tumor parameters after either proton or photon RT decreased significantly (p < 0.001). Among the 21 patients treated exclusively with proton RT, no significant increase in PVC-SUVmean or PVC-GLPG was observed in ipsilateral lungs after the PVC parameters of primary tumor were subtracted (p = 0.114 and p = 0.453, respectively). Also, there were no significant increases in SUVmean or GLG of contralateral lungs of patients who received proton RT (p = 0.841, p = 0.241, respectively). In contrast, among the nine patients who received photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001) and in GLG of contralateral (p = 0.036) lung. In the subset of nine patients who received a combined proton and photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001). CONCLUSION: Our data suggest less induction of inflammatory response in both the ipsilateral and contralateral lungs of patients treated with proton compared to photon or combined proton-photon RT.

Diagnostic manifestations of total hemispheric glucose metabolism ratio in neuronal network diaschisis: diagnostic implications in Alzheimer's disease and mild cognitive impairment.

PURPOSE: We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50-78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43-75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a "Network Diaschisis Test (NDT)". RESULTS: The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43-0.99), 0.86 (range 0.64-0.98), and 0.95 (range 0.65-1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18-0.98), 0.70 (range 0.48-0.81), and 0.84 (range 0.75-0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI. CONCLUSION: Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions.

Effect of blood glucose level on standardized uptake value (SUV) in 18F- FDG PET-scan: a systematic review and meta-analysis of 20,807 individual SUV measurements.

OBJECTIVES: To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in 18F-FDG-PET scan. METHODS: A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, 18F-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (< 110, 110-125, 125-150, 150-200, and > 200 mg/dl). RESULTS: Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p < 0.001, p < 0.001,) and muscle (p < 0.001, p < 0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p = 0.008, p < 0.001). No significant correlation was found between BGL and SUVmax or SUVmean in tumors. In the ANOVA test, all hyperglycemic groups had significantly lower SUVs compared with the euglycemic group in brain and muscle, and significantly higher SUVs in liver and blood pool. However, in tumors only the hyperglycemic group with BGL of > 200 mg/dl had significantly lower SUVmax. CONCLUSION: If BGL is lower than 200 mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.