Magnetic Resonance Positron Emission Tomography Research Articles

11C-Pittsburgh compound B and 18F-THK 5351 positron emission tomography brain imaging in cognitively normal individuals.

Abnormal beta-amyloid plaques and tau protein accumulation are the core pathologic features of Alzheimer's disease. However, the accumulation of these proteins is also common in cognitively normal elderly people. Therefore, this study is aimed to evaluate the amyloid and tau accumulation in the cognitively normal population. A preliminary prospective study was conducted on 24 cognitively normal individuals who underwent Pittsburgh compound B (11C-PiB) and 18F-THK 5351 positron emission tomography (PET)/computed tomography scans. The standardized uptake value ratio (SUVR) was used for quantitative analysis of the two tracers and comparisons between two age groups: ≤60 years and >60 years. Co-registration was applied between the dynamic acquisition PET and T1-weighted magnetic resonance imaging to delineate various cortical regions. P-mod software with the automated anatomical labeling-merged atlas was employed to generate automatic volumes of interest for different brain regions. The posterior cingulate versus precuneus SUVRs of PiB uptake was 1.40 ± 0.07 and 1.38 ± 0.22 versus 1.17 ± 0.07 and 1.14 ± 0.18 in those aged ≤60 years and >60 years, respectively, whereas the SUVRs of THK5351 retention at brain stem versus inferior temporal SUVRs were 1.84 ± 0.06 and 1.91 ± 0.18 versus 1.37 ± 0.04 and 1.48 ± 0.21 in the age groups of ≤ 60 years and >60 years, respectively (P = 0.20). Our findings allow the determination of the preliminary optimal cutoff points for SUVRs in amyloid and tau PET studies. Ultimately, these values can be applied to normal databases in clinical use to improve quantitative analysis.

Fluorodeoxyglucose positron-emission tomography-magnetic resonance hybrid imaging: An emerging tool for staging of cancer of the uterine cervix.

Positron-emission tomography-magnetic resonance imaging (PET-MRI) is an emerging hybrid imaging modality that utilizes the superior soft tissue resolution of MR with the metabolic data from PET. In this study, we sought to assess the clinical value of fluorodeoxyglucose (FDG) PET-MRI with dedicated pelvic PET-MR in the initial staging of cervical cancer. In this institutional-approved study, we identified 23 adult females who underwent FDG PET-MRI on hybrid camera for staging of primary uterine cervical cancer that included a dedicated PET-MR of the pelvis. A nuclear medicine physician and a radiologist reviewed the PET, MRI, and fusion-body and pelvis images alone and then with consensus read characterizing PET and MR abnormal findings. There were 23 patients who underwent FDG PET-MRI for initial staging of cervical cancer with an average age of 52.2 ± 14.0 years. A total of 23 suspected lymph nodes in eight different patients were detected within the pelvis with increased metabolic activity on PET. Both the dedicated pelvis and whole-body PET imaging detected the same corresponding pelvic lymph nodes, although the pelvic PET imaging had better lymph node uptake delineation due to longer acquisition time. Using a 10-mm short-axis criterion, MRI identified only 43.5% of the FDG avid lymph nodes. The average SUVmax on the pelvis PET sequences was higher with SUV 8.9 ± 5.2 compared to the whole-body PET with SUV 7.8 ± 5.4 but was not statistically significant (P > 0.05). Primary cervical cancer was identified in 18 patients on both PET imaging and MRI with dedicated MR pelvis providing better characterization. Based on our results of the patients with cervical cancer evaluated for initial staging, combining dedicated pelvic PET-MRI with whole-body PET/MR provides the most complete status of malignant disease in reference to delineation of primary tumor, involvement of surrounding tissues, and regional lymph nodes.

Evaluation of the Diagnostic Performance of Positron Emission Tomography/Magnetic Resonance for the Diagnosis of Liver Metastases.

The aim of this study was to compare the performance of positron emission tomography (PET)/magnetic resonance (MR) versus stand-alone PET and stand-alone magnetic resonance imaging (MRI) in the detection and characterization of suspected liver metastases. This multi-institutional retrospective performance study was approved by the institutional review boards and was Health Insurance Portability and Accountability Act compliant, with waiver of informed consent. Seventy-nine patients with confirmed solid extrahepatic malignancies who underwent upper abdominal PET/MR between February 2017 and June 2018 were included. Where focal hepatic lesions were identified, the likelihood of a diagnosis of a liver metastasis was defined on an ordinal scale for MRI, PET, and PET/MRI by 3 readers: 1 nuclear medicine physician and 2 radiologists. The number of lesions per patient, lesion size, and involved hepatic segments were recorded. Proof of metastases was based on histopathologic correlation or clinical/imaging follow-up. Diagnostic performance was assessed using sensitivity, specificity, positive and negative predictive values, and receiver operator characteristic curve analysis. A total of 79 patients (53 years, interquartile range, 50-68; 43 men) were included. PET/MR had a sensitivity of 95%, specificity of 97%, positive predictive value of 97%, and negative predictive value of 95%. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI were 88%, 98%, 98%, and 90% and for PET were 83%, 97%, 97%, and 86%, respectively. The areas under the curve for PET/MRI, MRI, and PET were 95%, 92%, and 92%, respectively. Contrast-enhanced PET/MR has a higher sensitivity and negative predictive value than either PET or MRI alone in the setting of suspected liver metastases. Fewer lesions were characterized as indeterminate by PET/MR in comparison with PET and MRI. This superior performance could potentially impact treatment and management decisions for patients with suspected liver metastases.

Head–Neck Cancer Delineation

Head–Neck Cancer (HNC) has a relevant impact on the oncology patient population and for this reason, the present review is dedicated to this type of neoplastic disease. In particular, a collection of methods aimed at tumor delineation is presented, because this is a fundamental task to perform efficient radiotherapy. Such a segmentation task is often performed on uni-modal data (usually Positron Emission Tomography (PET)) even though multi-modal images are preferred (PET-Computerized Tomography (CT)/PET-Magnetic Resonance (MR)). Datasets can be private or freely provided by online repositories on the web. The adopted techniques can belong to the well-known image processing/computer-vision algorithms or the newest deep learning/artificial intelligence approaches. All these aspects are analyzed in the present review and comparison among various approaches is performed. From the present review, the authors draw the conclusion that despite the encouraging results of computerized approaches, their performance is far from handmade tumor delineation result.

Evaluating the image quality of combined positron emission tomography-magnetic resonance images acquired in the pelvic radiotherapy position

Positron emission tomography-magnetic resonance (PET-MR) scanners could improve radiotherapy planning through combining PET and MR functional imaging. This depends on acquiring high quality and quantitatively accurate images in the radiotherapy position. This study evaluated PET-MR image quality using a flat couch and coil bridge for pelvic radiotherapy. MR and PET image quality phantoms were imaged in three setups: phantom on the PET-MR couch with anterior coil on top (diagnostic), phantom on a flat couch with coil on top (couch), and phantom on the flat couch with coil on a coil bridge (radiotherapy). PET images were also acquired in each setup without the anterior coil. PET attenuation correction of the flat couch and coil bridge were generated using kilovoltage computed tomography (CT) images and of the anterior coil using megavoltage CT images. MR image quality was substantially affected, with MR signal to noise ratio (SNR) relative to the diagnostic setup of 89% ± 2% (mean ± standard error of the mean, couch) and 54% ± 1% (radiotherapy), likely due to the increased distance between the patient and receive coils. The reduction impacted the low-contrast detectability score: 23 ± 1 (diagnostic), 19.7 ± 0.3 (couch) and 15 ± 1 (radiotherapy). All other MR metrics agreed within one standard error. PET quantitative accuracy was also affected, with measured activity with anterior coil being different to diagnostic without anterior coil by −16.7% ± 0.2% (couch) and −17.7 ± 0.1% (radiotherapy), without attenuation correction modification. Including the couch and coil bridge attenuation correction reduced this difference to −7.5% ± 0.1%, and including the anterior coil reduced this to −2.7% ± 0.1%. This was better than the diagnostic setup with anterior coil (difference −8.3% ± 0.2%). This translated into greater PET SNR performance for the fully corrected radiotherapy setup compared to diagnostic with coil. However contrast recovery was unchanged by the modified attenuation correction, with the diagnostic setup remaining ∼2% better. Quantitative PET in the radiotherapy setup is possible if appropriate attenuation correction is used. Pelvic radiotherapy PET-MR imaging protocols will need to consider the impact on PET-MR image quality.

Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease

Plasma phosphorylated tau at threonine 181 (p-tau181) has been proposed as an easily accessible biomarker for the detection of Alzheimer disease (AD) pathology, but its ability to monitor disease progression in AD remains unclear. To study the potential of longitudinal plasma p-tau181 measures for assessing neurodegeneration progression and cognitive decline in AD in comparison to plasma neurofilament light chain (NfL), a disease-nonspecific marker of neuronal injury. This longitudinal cohort study included data from the Alzheimer's Disease Neuroimaging Initiative from February 1, 2007, to June 6, 2016. Follow-up blood sampling was performed for up to 8 years. Plasma p-tau181 measurements were performed in 2020. This was a multicentric observational study of 1113 participants, including cognitively unimpaired participants as well as patients with cognitive impairment (mild cognitive impairment and AD dementia). Participants were eligible for inclusion if they had available plasma p-tau181 and NfL measurements and at least 1 fluorine-18-labeled fluorodeoxyglucose (FDG) positron emission tomography (PET) or structural magnetic resonance imaging scan performed at the same study visit. Exclusion criteria included any significant neurologic disorder other than suspected AD; presence of infection, infarction, or multiple lacunes as detected by magnetic resonance imaging; and any significant systemic condition that could lead to difficulty complying with the protocol. Plasma p-tau181 and NfL measured with single-molecule array technology. Longitudinal imaging markers of neurodegeneration (FDG PET and structural magnetic resonance imaging) and cognitive test scores (Preclinical Alzheimer Cognitive Composite and Alzheimer Disease Assessment Scale-Cognitive Subscale with 13 tasks). Data were analyzed from June 20 to August 15, 2020. Of the 1113 participants (mean [SD] age, 74.0 [7.6] years; 600 men [53.9%]; 992 non-Hispanic White participants [89.1%]), a total of 378 individuals (34.0%) were cognitively unimpaired (CU) and 735 participants (66.0%) were cognitively impaired (CImp). Of the CImp group, 537 (73.1%) had mild cognitive impairment, and 198 (26.9%) had AD dementia. Longitudinal changes of plasma p-tau181 were associated with cognitive decline (CU: r = -0.24, P < .001; CImp: r = 0.34, P < .001) and a prospective decrease in glucose metabolism (CU: r = -0.05, P = .48; CImp: r = -0.27, P < .001) and gray matter volume (CU: r = -0.19, P < .001; CImp: r = -0.31, P < .001) in highly AD-characteristic brain regions. These associations were restricted to amyloid-β-positive individuals. Both plasma p-tau181 and NfL were independently associated with cognition and neurodegeneration in brain regions typically affected in AD. However, NfL was also associated with neurodegeneration in brain regions exceeding this AD-typical spatial pattern in amyloid-β-negative participants. Mediation analyses found that approximately 25% to 45% of plasma p-tau181 outcomes on cognition measures were mediated by the neuroimaging-derived markers of neurodegeneration, suggesting links between plasma p-tau181 and cognition independent of these measures. Study findings suggest that plasma p-tau181 was an accessible and scalable marker for predicting and monitoring neurodegeneration and cognitive decline and was, unlike plasma NfL, AD specific. The study findings suggest implications for the use of plasma biomarkers as measures to monitor AD progression in clinical practice and treatment trials.

The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer's Disease.

Background Some studies have reported the effectiveness of [18F]PI-2620 as an effective tau-binding radiotracer; however, few reports have applied semiquantitative analysis to the tracer. Therefore, this study's aim was to perform a semiquantitative analysis of [18F]PI-2620 in individuals with normal cognition and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods Twenty-six cognitively normal (CN) subjects, 7 patients with AD, and 36 patients with MCI were enrolled. A dynamic positron emission tomography (PET) scan was performed 30–75 min postinjection. PET and T1-weighted magnetic resonance imaging scans were coregistered. The standardized uptake value ratio (SUVr) was used for semiquantitative analysis. The P-Mod software was applied to create volumes of interest. The ANOVA and post hoc Tukey HSD were used for statistical analysis. Results In the AD group, the occipital lobe had a significantly higher mean SUVr (1.46 ± 0.57) than in the CN and MCI groups. Compared with the CN group, the AD group showed significantly higher mean SUVr in the fusiform gyrus (1.06 ± 0.09 vs. 1.49 ± 0.86), inferior temporal (1.07 ± 0.07 vs. 1.46 ± 0.08), parietal lobe, lingual gyrus, and precuneus regions. Similarly, the AD group demonstrated a higher mean SUVr than the MCI group in the precuneus, lingual, inferior temporal, fusiform, supramarginal, orbitofrontal, and superior temporal regions. The remaining observed regions, including the striatum, basal ganglia, thalamus, and white matter, showed a low SUVr across all groups with no statistically significant differences. Conclusion A significantly higher mean SUVr of [18F]PI-2620 was observed in the AD group; a significant area of the brain in the AD group demonstrated tau protein deposit in concordance with Braak Stages III–V, providing useful information to differentiate AD from CN and MCI. Moreover, the low SUVr in the deep striatum and thalamus could be useful for excluding primary tauopathies.

Lanabecestat: Neuroimaging results in early symptomatic Alzheimer's disease.

IntroductionLanabecestat, a beta‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) inhibitor, was investigated as a potential Alzheimer's disease (AD)‐modifying treatment. As previously reported, amyloid beta (Aβ) neuritic plaque burden reduction did not result in clinical benefit. Lanabecestat's effects on neuroimaging biomarkers and correlations between neuroimaging biomarkers and efficacy measures are reported.MethodsAMARANTH and DAYBREAK‐ALZ were 104‐ and 78‐week, multicenter, randomized, double‐blind, placebo‐controlled studies of lanabecestat in early symptomatic AD (AMARANTH) and mild AD dementia (DAYBREAK‐ALZ). Patients randomly (1:1:1) received placebo, lanabecestat 20 mg, or lanabecestat 50 mg daily (AMARANTH, n = 2218; DAYBREAK‐ALZ, n = 1722). Florbetapir positron emission tomography (PET), fluorodeoxyglucose (FDG) PET, flortaucipir PET, and volumetric magnetic resonance imaging (MRI) were used to measure Aβ neuritic plaque burden, cerebral metabolism, aggregated tau neurofibrillary tangles, and brain volume, respectively. Additionally, florbetapir perfusion scans were performed in DAYBREAK‐ALZ. Efficacy measures included 13‐item Alzheimer's Disease Assessment Scale–Cognitive Subscale, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, Clinical Dementia Rating–Sum of Boxes, Functional Activities Questionnaire, and Mini‐Mental State Examination. These studies stopped early due to futility.ResultsDespite previously observed annualized reduction in Aβ neuritic plaque burden, there were no treatment differences in annualized change of aggregated tau neurofibrillary tangle burden (AMARANTH, n = 284; DAYBREAK‐ALZ, n = 70), cerebral metabolism (AMARANTH, n = 260; DAYBREAK‐ALZ, n = 38) and perfusion (DAYBREAK‐ALZ, n = 213). Greater brain volume reduction (AMARANTH, n = 1697 [whole brain]; DAYBREAK‐ALZ, n = 650 [whole brain]) occurred on lanabecestat compared to placebo. Higher baseline aggregated tau neurofibrillary tangle burden, lower cerebral metabolism, and lower brain volumes correlated with poorer baseline efficacy scores and greater clinical worsening. Lower baseline cerebral perfusion correlated with poorer baseline efficacy scores. Reduction in cerebral metabolism or whole brain volume correlated with clinical worsening, regardless of treatment assignment.DiscussionTau pathology and cerebral metabolism assessments showed no evidence of lanabecestat slowing pathophysiologic progression of AD. Lanabecestat exposure was associated with brain volume reductions. Correlations between imaging measures and cognitive assessments may aid future study design.

No evidence for brown adipose tissue activation after creatine supplementation in adult vegetarians.

Creatine availability in adipose tissue has been shown to have profound effects on thermogenesis and energy balance in mice. However, whether dietary creatine supplementation affects brown adipose tissue (BAT) activation in humans is unclear. In the present study, we report the results of a double-blind, randomized, placebo-controlled, cross-over trial (NCT04086381) in which 14 young, healthy, vegetarian adults, who are characterized by low creatine levels, received 20 g of creatine monohydrate per day or placebo. Participants were eligible if they met the following criteria: male or female, white, aged 18-30 years, consuming a vegetarian diet (≥6 months) and body mass index 20-25 kg m-2. BAT activation after acute cold exposure was determined by calculating standard uptake values (SUVs) acquired by [18F]fluorodeoxyglucose positron emission tomography-magnetic resonance imaging. BAT volume (-31.32 (19.32) SUV (95% confidence interval (CI) -73.06, 10.42; P = 0.129)), SUVmean (-0.34 (0.29) SUV (95% CI -0.97, 0.28; P = 0.254)) and SUVmax (-2.49 (2.64) SUV (95% CI -8.20, 3.21; P = 0.362)) following acute cold exposure were similar between placebo and creatine supplementation. No side effects of creatine supplementation were reported; one participant experienced bowel complaints during placebo, which resolved without intervention. Our data show that creatine monohydrate supplementation in young, healthy, lean, vegetarian adults does not enhance BAT activation after acute cold exposure.

Alterations in resting-state network dynamics along the Alzheimer\u2019s disease continuum

Human brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimer's disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD. We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with subjective cognitive decline (SCD), 10 patients with amnestic mild cognitive impairment (aMCI) and 10 patients with typical Alzheimer’s disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. Correlations were sought between temporal properties of HMM states and participants' cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism. The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores, nor with the whole hippocampal volume. However, it correlated positively with the regional glucose consumption in the right dorsolateral prefrontal cortex (DLPFC). AD patients present alterations of posterior DMN power activation dynamics at rest that identify an additional electrophysiological correlate of AD-related synaptic and neural dysfunction. The right DLPFC may play a causal role in the activation of the posterior DMN, possibly linked to the occurrence of mind wandering episodes. As such, these data might suggest a neural correlate of the decrease in mind wandering episodes reported in pathological aging.

FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome.

Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. To investigate if individual brain [18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [11 C]Pittsburgh Compound-B (PIB)-PET. Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. © 2020 International Parkinson and Movement Disorder Society.

Positron Emission Tomography-Magnetic Resonance Imaging Pharmacokinetics, In Vivo Biodistribution, and Whole-Body Elimination of Mn-PyC3A.

Mn-PyC3A is an experimental manganese (Mn)-based extracellular fluid magnetic resonance imaging (MRI) contrast agent that is being evaluated as a direct replacement for clinical gadolinium (Gd)-based contrast agents. The goals of this study were to use simultaneous positron emission tomography (PET)-MRI to (1) compare the whole-body pharmacokinetics, biodistribution, and elimination of Mn-PyC3A with the liver-specific contrast agent mangafodipir (Mn-DPDP), (2) determine the pharmacokinetics and fractional excretion of Mn-PyC3A in a rat model of renal impairment, and (3) compare whole-body elimination of Mn-PyC3A to gadoterate (Gd-DOTA) in a rat model of renal impairment. Mn-PyC3A and Mn-DPDP were radiolabeled with the positron emitting isotope Mn-52 via Mn2+ exchange with 52MnCl2. Dynamic simultaneous PET-MRI was used to measure whole-body pharmacokinetics and biodistribution of Mn-52 immediately and out to 7 days after an intravenous 0.2 mmol/kg dose of [52Mn]Mn-PyC3A to normal or to 5/6 nephrectomy rats or a 0.01 mmol/kg dose of [52Mn]Mn-DPDP to normal rats. The fractional excretion and 1- and 7-day biodistribution in rats after the injection of 2.0 mmol/kg [52Mn]Mn-PyC3A (n = 11 per time point) or 2.0 mmol/kg Gd-DOTA (n = 8 per time point) were quantified by gamma counting or Gd elemental analysis, respectively. Comparisons of Mn-PyC3A pharmacokinetics and in vivo biodistribution in normal and 5/6 nephrectomy rats and comparisons of ex vivo Mn versus Gd biodistribution data in 5/6 nephrectomy were made with an unpaired t test. Dynamic PET-MRI data demonstrate that both [52Mn]Mn-PyC3A and [52Mn]Mn-DPDP were eliminated by mixed renal and hepatobiliary elimination but that a greater fraction of [52Mn]Mn-PyC3A was eliminated by renal filtration. Whole-body PET images show that Mn-52 from [52Mn]Mn-PyC3A was efficiently eliminated from the body, whereas Mn-52 from [52Mn]Mn-DPDP was retained throughout the body. The blood elimination half-life of [52Mn]Mn-PyC3A in normal and 5/6 nephrectomy rats was 13 ± 3.5 minutes and 23 ± 12 minutes, respectively (P = 0.083). Area under the curve between 0 and 60 minutes postinjection (AUC0-60) in the bladder of normal and 5/6 nephrectomy rats was 2600 ± 1700 %ID/cc*min and 750 ± 180 %ID/cc*min, respectively (P = 0.024), whereas AUC0-60 in the liver of normal and 5/6 nephrectomy rats was 33 ± 13 %ID/cc*min and 71 ± 16 %ID/cc*min, respectively (P = 0.011), indicating increased hepatobiliary elimination in 5/6 nephrectomy rats. The %IDs of Mn from [52Mn]Mn-PyC3A and Gd from Gd-DOTA recovered from 5/6 nephrectomy rats 1 day after injection were 2.0 ± 1.1 and 1.3 ± 0.34, respectively (P = 0.10) and 7 days after injection were 0.14 ± 0.11 and 0.41 ± 0.24, respectively (P = 0.0041). Mn-PyC3A has different pharmacokinetics and is more efficiently eliminated than Mn-DPDP in normal rats. Mn-PyC3A is efficiently eliminated from both normal and 5/6 nephrectomy rats, with increased fractional hepatobiliary excretion from 5/6 nephrectomy rats. Mn-PyC3A is more completely eliminated than Gd-DOTA from 5/6 nephrectomy rats after 7 days.

Age-dependent cardiac remodelling – role of sex hormones

Abstract Background While cardiovascular mortality in women has exceeded those in men, women continue to be underrepresented in cardiovascular clinical trials. Further, preclinical experiments are predominantly conducted in male animals, rendering sex-specific variables contributing to cardiovascular disease largely unknown. As age and menopause remain to be key risk factors for cardiovascular disease in women, the aim of this study was to identify key variables of cardiac remodelling in the aging female and male heart, as well as to assess effects of sex hormone deprivation on left ventricular (LV) morphology, LV function and cardiac sympathetic activity. Materials and methods Gonadectomized and sham-operated FVB/N mice of both sexes were subjected to positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging at the age of 4 (young cohort) and 20 (aged cohort) months (total n=123, 55% females). Following tail-vein injection of [11C]meta-hydroxynorephedrine ([11C]mHED), a widely used PET probe in preclinical and clinical assessment of cardiac sympathetic integrity, animals were scanned and cardiac sympathetic outflow was derived from myocardial [11C]mHED uptake. Cardiac parameters including LV volumes and left ventricular ejection fraction (LVEF) were obtained from electrocardiogram (ECG)-gated CMR imaging. Results and discussion A significant increase of LVEF was observed in aging females (p=0.012, Figure 1), but not in males. The latter was not associated with a higher cardiac output, and was a consequence of reduced LV end-systolic volumes (p=0.008), unveiling a substantial reduction of size in the aging female heart. As this age-dependent observation was not present in gonadectomized animals (p=0.414), the lack of growth-stimulating estrogen might account for reduction of cardiac size in aging females. Thus, despite a significantly heightened body weight, female heart size is reduced with age. Accordingly, sufficient cardiac output was maintained via increased heart rate (p=0.005) and cardiac sympathetic activity (p=0.040, Figure 1). Gonadectomy accelerated age-dependent changes in LV morphology and function in female mice. While sex hormone deprivation blunted cardiac sympathetic activity and norepinephrine levels in male mice, an opposite trend was observed in females. Conclusion Despite increasing body weight with age, aged female and male hearts maintain a stable circulatory blood supply, however, by distinct mechanisms. While the “shrinking” female heart requires an increased heart rate and cardiac sympathetic activity to compensate for smaller ventricular volumes, aging males maintain cardiac size. Importantly, sex hormone deprivation at a young age accelerates age-dependent changes in LV morphology and function in female mice, but not in male mice. The increased sympathetic activity reflects a higher stress level in aged females that might expose them to a higher cardiac vulnerability at postmenopausal age. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation; Swissheart Foundation

Adenosine stress native T1 mapping demonstrates impaired myocardial perfusion reserve in non-ischemic dilated cardiomyopathy

Abstract Background Impaired myocardial perfusion reserve has been demonstrated in non-ischemic dilated cardiomyopathy (NIDCM) by positron emission tomography (PET) and adenosine-stress first-pass perfusion cardiac magnetic resonance (CMR) imaging. Adenosine stress native T1 mapping is a novel CMR technique able to assess myocardial perfusion without the use of contrast agents. The aim of the present study was to determine the clinical utility of this novel CMR technique in NIDCM. Methods A total of 20 consecutive patients (mean age 61±12 years, 80% males) with diagnosis of NIDCM who consented to be enrolled in the UHSM CMR registry were included in the present study. CMR at 3T including 1. cine imaging for the assessment of LV volumes, mass and global longitudinal strain (GLS) by tissue-tracking imaging; 2. rest and stress (adenosine 140 mcg/kg/min) MOLLI T1 mapping of mid-ventricular slice for the assessment of rest and stress T1 values and T1 reactivity (ΔT1%); 3. first-pass perfusion imaging for the assessment of myocardial perfusion reserve index (MPRI) and 4. late gadolinium enhancement (LGE) imaging for the assessment of myocardial replacement fibrosis, was performed. Twenty control patients without history of known coronary artery disease and evidence of reversible ischemia or previous myocardial infarct on CMR imaging were included for comparison purposes. Results NIDCM patients had significantly higher native T1 value (1263±47 ms vs. 1234±38 ms, p=0.031), significantly lower ΔT1% (3.2±1.5% vs. 5.7±1.7%, p&amp;lt;0.001, Figure A), significantly lower MPRI (1.32±0.18 vs. 1.67±0.13, p&amp;lt;0.001) and significantly impaired GLS (−10±4% vs. −16±2%, p&amp;lt;0.001) as compared to controls. A significant strong relation between ΔT1% and MPRI (β=0.76, p&amp;lt;0.001, Figure B) and significant moderate relation between ΔT1% and GLS (β=−0.54, p&amp;lt;0.001) were observed. Conclusion T1 reactivity, myocardial perfusion reserve and GLS are significantly reduced in NIDCM patients compared to controls. Adenosine stress T1 mapping holds promise for detection of impaired myocardial perfusion reserve in NIDCM without the requirement for contrast agents. Funding Acknowledgement Type of funding source: None

Improving staging of rectal cancer in the pelvis: the role of PET/MRI.

The role of positron emission tomography/magnetic resonance (PET/MR) in evaluating the local extent of rectal cancer remains uncertain. This study aimed to investigate the possible role of PET/MR versus magnetic resonance (MR) in clinically staging rectal cancer. This retrospective two-center cohort study of 62 patients with untreated rectal cancer investigated the possible role of baseline staging PET/MR versus stand-alone MR in determination of clinical stage. Two readers reviewed T and N stage, mesorectal fascia involvement, tumor length, distance from the anal verge, sphincter involvement, and extramural vascular invasion (EMVI). Sigmoidoscopy, digital rectal examination, and follow-up imaging, along with surgery when available, served as the reference standard. PET/MR outperformed MR in evaluating tumor size (42.5 ± 21.03mm per the reference standard, 54 ± 20.45mm by stand-alone MR, and 44 ± 20mm by PET/MR, P = 0.004), and in identifying N status (correct by MR in 36/62 patients [58%] and by PET/MR in 49/62 cases [79%]; P = 0.02) and external sphincter infiltration (correct by MR in 6/10 and by PET/MR in 9/10; P = 0.003). No statistically significant differences were observed in relation to any other features. PET/MR provides a more precise assessment of the local extent of rectal cancers in evaluating cancer length, N status, and external sphincter involvement. PET/MR offers the opportunity to improve clinical decision-making, especially when evaluating low rectal tumors with possible external sphincter involvement.

Additional value of hybrid PET/MR imaging versus MR or PET performed separately to assess cardiovascular disease

Introduction and objectivesHybrid positron emission tomography (PET) and magnetic resonance (MR) imaging is an emerging technology in the diagnosis of cardiovascular disease; however, there have been no reports of its use in the national clinical setting. Our objective was to evaluate the additional value of integrated PET/MR systems compared with MR and PET performed separately in this setting. MethodsWe prospectively included 49 patients, 30 to assess myocardial viability (coronary group) and 19 to assess inflammatory, infectious, and tumoral diseases (noncoronary heart disease group). All patients underwent cardiac 18F-fluorodeoxyglucose PET/MR. PET/MR studies included attenuation correction sequences, followed by simultaneous cardiac PET and cardiac MR acquisition, with protocols adapted to the clinical indication (cine, tissue characterization and/or late enhancement imaging). ResultsMost (87.8%) PET/MR studies were initially interpretable. Use of PET/MR improved diagnosis vs PET or MR performed separately in 42.1% of coronary cases and 88.9% of noncoronary cases. PET/MR enabled reclassification of 87.5% of coronary cases initially classified as showing inconclusive results on MR or PET and 70% of noncoronary cases. ConclusionsIn our series, multimodality PET/MR technology provided additional diagnostic value in some patients with cardiovascular disease compared with MR and PET performed separately, especially in cases of noncoronary heart disease and in those with inconclusive results on MR or PET. In our experience, the main benefits of PET/MR include the possibility of simultaneous acquisition, the in vivo integration of anatomical/functional/metabolic aspects, and the interaction of different experts in imaging modalities.

Degeneration of gray and white matter differs between hypometabolic and hypermetabolic brain regions in a patient with ALS-FTD: a longitudinal MRI − PET multimodal study

Objective [18F]-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET) imaging and magnetic resonance imaging (MRI) of brain in ALS patients with frontotemporal lobe dementia (ALS-FTD) reveal hypometabolism and hypermetabolism, as well as gray matter (GM) and white matter (WM) abnormalities in different brain regions, respectively. Hypometabolism arising from neuronal dysfunction or loss is the most recognized pathophysiologic change in neurodegeneration, whereas mechanisms underlying hypermetabolism remain unclear. We hypothesize that hypometabolic and hypermetabolic brain regions in ALS-FTD represent differential degeneration of GM and WM structures, as revealed by co-registered MRI in a two time-point longitudinal multimodal study. Methods: A 69-year-old female with ALS-FTD underwent 18F-FDG PET, diffusion tensor imaging (DTI), and T1-weighted MRI at baseline (15 months after symptom onset), and 20.4 months later. Cerebral glucose metabolism rate, cortical thickness, cortical area, and WM network changes were measured longitudinally. Results and conclusion: The patient had symptoms and signs of bulbar-onset upper motor neuron (UMN)-predominant ALS with language and behavioral dysfunction. Evaluation at baseline showed bulbar dysfunction, and impaired language and executive function. At follow-up, worsened bulbar and other motor functions, and prominent FTD both reflected significant progression. Cortical thickness and surface area showed differential involvement in the hypometabolic and hypermetabolic regions. WM connections from frontal regions to other brain regions were completely absent by graph theory-based network analysis when compared to temporal regions indicating prominent frontal lobe degeneration. Structural neuroimaging reveals different patterns of GM and WM involvement in the hypometabolic and hypermetabolic brain regions in a patient with ALS-FTD.

GBA Variants in Parkinson's Disease: Clinical, Metabolomic, and Multimodal Neuroimaging Phenotypes.

Alterations in the GBA gene (NM_000157.3) are the most important genetic risk factor for Parkinson's disease (PD). Biallelic GBA mutations cause the lysosomal storage disorder Gaucher's disease. The GBA variants p.E365K and p.T408M are associated with PD but not with Gaucher's disease. The pathophysiological role of these variants needs to be further explored. This study analyzed clinical, neuropsychological, metabolic, and neuroimaging phenotypes of patients with PD carrying the GBA variants p.E365K and p.T408M. GBA was sequenced in 56 patients with mid-stage PD. Carriers of GBA variants were compared with noncarriers regarding clinical history and symptoms, neuropsychological features, metabolomics, and multimodal neuroimaging. Blood plasma gas chromatography coupled to mass spectrometry, 6-[18 F]fluoro-L-Dopa positron emission tomography (PET), [18 F]fluorodeoxyglucose PET, and resting-state functional magnetic resonance imaging were performed. Sequence analysis detected 13 heterozygous GBA variant carriers (7 with p.E365K, 6 with p.T408M). One patient carried a GBA mutation (p.N409S) and was excluded. Clinical history and symptoms were not significantly different between groups. Global cognitive performance was lower in variant carriers. Metabolomic group differences were suggestive of more severe PD-related alterations in carriers versus noncarriers. Both PET scans showed signs of a more advanced disease; [18 F]fluorodeoxyglucose PET and functional magnetic resonance imaging showed similarities with Lewy body dementia and PD dementia in carriers. This is the first study to comprehensively assess (neuro-)biological phenotypes of GBA variants in PD. Metabolomics and neuroimaging detected more significant group differences than clinical and behavioral evaluation. These alterations could be promising to monitor effects of disease-modifying treatments targeting glucocerebrosidase metabolism. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Isolated metachronous splenic multiple metastases after colon cancer surgery: A case report and literature review

BACKGROUNDIsolated splenic metastasis is a rare clinical entity. Multiple metastases in the spleen after radical colon resection in a patient who subsequently underwent a second local resection for isolated metachronous splenic metastasis are exceedingly rare.CASE SUMMARYWe report a colon cancer patient who underwent laparoscopic radical colon resection 14 mo previously, and subsequently underwent a second local resection due to local recurrence detected by elevated serum carcinoembryonic antigen (CEA) and positron emission tomography (PET). However, multiple metastases in the spleen were found 7 mo later by elevated serum CEA and PET-magnetic resonance imaging. Then the patient underwent total laparoscopic splenectomy. Local tumor recurrence and splenic metastasis from colorectal cancer (CRC) were found by postoperative pathology. Genetic analysis of these recurrent and metastatic tissues showed KRAS exon2, APC exon16 and TP53 exon6 missense mutations, but no mutations of NRAS, KRAF, EGFR, ERBB2, MET, MLH1, MSH2 and MSH6 were detected. Chemotherapy and target therapy were administered after multiple disciplinary team (MDT) consultation, and no tumor recurrence has been observed to date. We also reviewed the literature by conducting a search of the PubMed database using the following key words: CRC, splenic metastasis, isolated, and review. We identified 34 relevant papers, which included 28 cases of metachronous metastasis and 6 cases of simultaneous metastasis.CONCLUSIONClose monitoring of serum CEA levels is crucial for the detection of isolated splenic metastases after colon surgery. In terms of overall survival and progression-free survival, MDT plays an important role in the entire process of disease management.

Diagnostic Performance of PET Imaging Using Different Radiopharmaceuticals in Prostate Cancer According to Published Meta-Analyses.

A significant number of meta-analyses reporting data on the diagnostic performance of positron emission tomography (PET) in prostate cancer (PCa) is currently available in the literature. In particular, different PET radiopharmaceuticals were used for this purpose. The aim of this review is to summarize information retrieved by published meta-analyses on this topic. The first step included a systematic search of the literature (last search date: June 2020), screening two databases (PubMed/MEDLINE and Cochrane Library). This combination of key words was used: (A) “PET” OR “positron emission tomography” AND (B) “prostate” OR “prostatic” AND (C) meta-analysis. Only meta-analyses on Positron Emission Tomography/Computed Tomography (PET/CT) or Positron Emission Tomography/Magnetic Resonance (PET/MR) in PCa were selected. We have summarized the diagnostic performance of PET imaging in PCa, taking into account 39 meta-analyses published in the literature. Evidence-based data showed the good diagnostic performance of PET/CT with several radiopharmaceuticals, including prostate-specific membrane antigen (PSMA)-targeted agents, radiolabeled choline, fluciclovine, and fluoride in restaging and staging settings. Less evidence-based data were available for PET/MR with different radiotracers. More prospective multicentric studies and cost-effectiveness analyses are warranted.