Magnetic resonance imaging as a noninvasive adjunct to conventional assessment of functional differences between kidneys in vivo and during ex vivo normothermic machine perfusion.

Normothermic machine perfusion (NMP) is increasingly considered for pretransplant kidney quality assessment. However, fundamental questions about differences between in vivo and ex vivo renal function, as well as the impact of ischemic injury on ex vivo physiology, remain unanswered. This study utilized magnetic resonance imaging (MRI), alongside conventional parameters to explore differences between in vivo and ex vivo renal function and the impact of warm ischemia on a kidney's behavior ex vivo. Renal MRI scans and samples were obtained from living pigs (n = 30) in vivo. Next, kidney pairs were procured and exposed to minimal, or 75 minutes of warm ischemia, followed by 6 hours of hypothermic machine perfusion. Both kidneys simultaneously underwent 6-hour ex vivo perfusion in MRI-compatible NMP circuits to obtain multiparametric MRI data. Ischemically injured ex vivo kidneys showed a significantly altered regional blood flow distribution compared to in vivo and minimally damaged organs. Both ex vivo groups showed diffusion restriction relative to in vivo. Our findings underscore the differences between in vivo and ex vivo MRI-based renal characteristics. Therefore, when assessing organ viability during NMP, it should be considered to incorporate parameters beyond the conventional functional markers that are common in vivo.

Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT-SEQUOIA.

BACKGROUND: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time-consuming and labor-intensive. PURPOSE: To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low-dose computed tomography (LDCT) as an anatomical reference for PET-assessed vascular disease. METHODS: A software pipeline was developed including automated segmentation using a 3D U-Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U-Net, 352 non-contrast LDCTs from (2-[18 F]FDG and Na[18 F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold-out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values. RESULTS: Fully automated segmentation of the aorta using a 3D U-Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6-1.4] mm, similar to an open-source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0-1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00-1.00] and 0.99 [0.93-1.00] for calcium and uptake values, respectively). CONCLUSIONS: We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG-CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring.

Small vessel disease burden and functional brain connectivity in mild cognitive impairment.

Background: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing. Method: Functional brain connectivity differences were analyzed between mild cognitive impairment individuals with absent or low (n = 34) and high (n = 34) small vessel disease burden using data from the Parelsnoer Institute, a Dutch multicenter study. Small vessel disease was characterized using an ordinal scale considering: lacunes, microbleeds, perivascular spaces in the basal ganglia, and white matter hyperintensities. Resting state functional MRI data using 3 Tesla scanners was analyzed with group-independent component analysis using the CONN toolbox. Results: Functional connectivity between areas of the cerebellum and between the cerebellum and the thalamus and caudate nucleus was higher in the absent or low small vessel disease group compared to the high small vessel disease group. Conclusion: These findings might suggest that functional connectivity of mild cognitive impairment individuals with low or absent small vessel disease burden is more intact than in mild cognitive impairment individuals with high small vessel disease. These brain areas are mainly responsible for motor, attentional and executive functions, domains which in previous studies were found to be mostly associated with small vessel disease markers. Our results support findings on the involvement of the cerebellum in cognitive functioning.

Automated magnetic resonance imaging quantification of cerebral parenchymal and ventricular volume following subarachnoid hemorrhage: associations with cognition.

This study aims to investigate cerebral parenchymal and ventricular volume changes after subarachnoid hemorrhage (SAH) and their potential association with cognitive impairment. 17 patients with aneurysmal SAH (aSAH) and 21 patients with angiographically negative SAH (anSAH) without visually apparent parenchymal loss on conventional magnetic resonance imaging (MRI) were included, along with 76 healthy controls. Volumetric analyses were performed using an automated clinical segmentation and quantification tool. Measurements were compared to on-board normative reference database (n = 1923) adjusted for age, sex, and intracranial volume. Cognition was assessed with tests for psychomotor speed, attentional control, (working) memory, executive functioning, and social cognition. All measurements took place 5 months after SAH. Lower cerebral parenchymal volumes were most pronounced in the frontal lobe (aSAH: n = 6 [35%], anSAH n = 7 [33%]), while higher volumes were most substantial in the lateral ventricle (aSAH: n = 5 [29%], anSAH n = 9 [43%]). No significant differences in regional brain volumes were observed between both SAH groups. Patients with lower frontal lobe volume exhibited significantly lower scores in psychomotor speed (U = 81, p = 0.02) and attentional control (t = 2.86, p = 0.004). Additionally, higher lateral ventricle volume was associated with poorer memory (t = 3.06, p = 0.002). Regional brain volume changes in patients with SAH without visible parenchymal abnormalities on MRI can still be quantified using a fully automatic clinical-grade tool, exposing changes which may contribute to cognitive impairment. Therefore, it is important to provide neuropsychological assessment for both SAH groups, also including those with clinically mild symptoms.

Quantification of P-glycoprotein function at the human blood-brain barrier using [18F]MC225 and PET.

INTRODUCTION: P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease, and with drug-resistance, for example in treatment-resistant depression. The most widely used approach to measure P-gp function in vivo is (R)-[11C]verapamil PET. (R)-[11C]verapamil is, however, an avid P-gp substrate, which complicates the use of this tracer to measure an increase in P-gp function as its baseline uptake is already very low. [18F]MC225 was developed to measure both increases and decreases in P-gp function. AIM: The aim of this study was (1) to identify the pharmacokinetic model that best describes [18F]MC225 kinetics in the human brain and (2) to determine test-retest variability. METHODS: Five (2 male, 3 female) of fourteen healthy subjects (8 male, 6 female, age 67 ± 5 years) were scanned twice (injected dose 201 ± 47 MBq) with a minimum interval of 2 weeks between scans. Each scanning session consisted of a 60-min dynamic [18F]MC225 scan with continuous arterial sampling. Whole brain grey matter data were fitted to a single tissue compartment model, and to reversible and irreversible two tissue-compartment models to obtain various outcome parameters (in particular the volume of distribution (VT), Ki, and the rate constants K1 and k2). In addition, a reversible two-tissue compartment model with fixed k3/k4 was included. The preferred model was selected based on the weighted Akaike Information Criterion (AIC) score. Test-retest variability (TRTV) was determined to assess reproducibility. RESULTS: Sixty minutes post-injection, the parent fraction was 63.8 ± 4.0%. The reversible two tissue compartment model corrected for plasma metabolites with an estimated blood volume (VB) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the VT for [18F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model. CONCLUSION: [18F]MC225 VT, derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%. TRIAL REGISTRATION: EudraCT 2020-001564-28 . Registered 25 May 2020.

Effects of proton therapy on regional [18F]FDG uptake in non-tumor brain regions of patients treated for head and neck cancer.

Background and purpose: Previous pre-clinical research using [18F]FDG-PET has shown that whole-brain photon-based radiotherapy can affect brain glucose metabolism. This study, aimed to investigate how these findings translate into regional changes in brain [18F]FDG uptake in patients with head and neck cancer treated with intensity-modulated proton therapy (IMPT). Materials and methods: Twenty-three head and neck cancer patients treated with IMPT and available [18F]FDG scans before and at 3 months follow-up were retrospectively evaluated. Regional assessment of the [18F]FDG standardized uptake value (SUV) parameters and radiation dose in the left (L) and right (R) hippocampi, L and R occipital lobes, cerebellum, temporal lobe, L and R parietal lobes and frontal lobe were evaluated to understand the relationship between regional changes in SUV metrics and radiation dose. Results: Three months after IMPT, [18F]FDG brain uptake calculated using SUVmean and SUVmax, was significantly higher than that before IMPT. The absolute SUVmean after IMPT was significantly higher than before IMPT in seven regions of the brain (p ≤ 0.01), except for the R (p = 0.11) and L (p = 0.15) hippocampi. Absolute and relative changes were variably correlated with the regional maximum and mean doses received in most of the brain regions. Conclusion: Our findings suggest that 3 months after completion of IMPT for head and neck cancer, significant increases in the uptake of [18F]FDG (reflected by SUVmean and SUVmax) can be detected in several individual key brain regions, and when evaluated jointly, it shows a negative correlation with the mean dose. Future studies are needed to assess whether and how these results could be used for the early identification of patients at risk for adverse cognitive effects of radiation doses in non-tumor tissues.

Magnetic resonance imaging during warm ex vivo kidney perfusion.

BACKGROUND: The shortage of donor organs for transplantation remains a worldwide problem. The utilization of suboptimal deceased donors enlarges the pool of potential organs, yet consequently, clinicians face the difficult decision of whether these sub-optimal organs are of sufficient quality for transplantation. Novel technologies could play a pivotal role in making pre-transplant organ assessment more objective and reliable. METHODS: Ex vivo normothermic machine perfusion (NMP) at temperatures around 35-37°C allows organ quality assessment in a near-physiological environment. Advanced magnetic resonance imaging (MRI) techniques convey unique information about an organ's structural and functional integrity. The concept of applying magnetic resonance imaging during renal normothermic machine perfusion is novel in both renal and radiological research and we have developed the first MRI-compatible NMP setup for human-sized kidneys. RESULTS: We were able to obtain a detailed and real-time view of ongoing processes inside renal grafts during ex vivo perfusion. This new technique can visualize structural abnormalities, quantify regional flow distribution, renal metabolism, and local oxygen availability, and track the distribution of ex vivo administered cellular therapy. CONCLUSION: This platform allows for advanced pre-transplant organ assessment, provides a new realistic tool for studies into renal physiology and metabolism, and may facilitate therapeutic tracing of pharmacological and cellular interventions to an isolated kidney.

Interpretation of pre-morbid cardiac 3T MRI findings in overweight and hypertensive young adults.

In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27-41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%-ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable.

Shortened duration whole body 18F-FDG PET Patlak imaging on the Biograph Vision Quadra PET/CT using a population-averaged input function.

BACKGROUND: Excellent performance characteristics of the Vision Quadra PET/CT, e.g. a substantial increase in sensitivity, allow for precise measurements of image-derived input functions (IDIF) and tissue time activity curves. Previously we have proposed a method for a reduced 30 min (as opposed to 60 min) whole body 18F-FDG Patlak PET imaging procedure using a previously published population-averaged input function (PIF) scaled to IDIF values at 30-60 min post-injection (p.i.). The aim of the present study was to apply this method using the Vision Quadra PET/CT, including the use of a PIF to allow for shortened scan durations. METHODS: Twelve patients with suspected lung malignancy were included and received a weight-based injection of 18F-FDG. Patients underwent a 65-min dynamic PET acquisition which were reconstructed using European Association of Nuclear Medicine Research Ltd. (EARL) standards 2 reconstruction settings. A volume of interest (VOI) was placed in the ascending aorta (AA) to obtain the IDIF. An external PIF was scaled to IDIF values at 30-60, 40-60, and 50-60 min p.i., respectively, and parametric 18F-FDG influx rate constant (Ki) images were generated using a t* of 30, 40 or 50 min, respectively. Herein, tumour lesions as well as healthy tissues, i.e. liver, muscle tissue, spleen and grey matter, were segmented. RESULTS: Good agreement between the IDIF and corresponding PIF scaled to 30-60 min p.i. and 40-60 min p.i. was obtained with 7.38% deviation in Ki. Bland-Altman plots showed excellent agreement in Ki obtained using the PIF scaled to the IDIF at 30-60 min p.i. and at 40-60 min p.i. as all data points were within the limits of agreement (LOA) (- 0.004-0.002, bias: - 0.001); for the 50-60 min p.i. Ki, all except one data point fell in between the LOA (- 0.021-0.012, bias: - 0.005). CONCLUSIONS: Parametric whole body 18F-FDG Patlak Ki images can be generated non-invasively on a Vision Quadra PET/CT system. In addition, using a scaled PIF allows for a substantial (factor 2 to 3) reduction in scan time without substantial loss of accuracy (7.38% bias) and precision (image quality and noise interference).

Investigating Recovery After Subarachnoid Hemorrhage With the Imaging, Cognition and Outcome of Neuropsychological Functioning After Subarachnoid Hemorrhage (ICONS) Study: Protocol for a Longitudinal, Prospective Cohort Study.

BACKGROUND: A subarachnoid hemorrhage is a hemorrhage in the subarachnoid space that is often caused by the rupture of an aneurysm. Patients who survive a subarachnoid hemorrhage have a high risk of complications and a negative long-term outcome. OBJECTIVE: The aim of the Imaging, Cognition and Outcome of Neuropsychological functioning after Subarachnoid hemorrhage (ICONS) study is to investigate whether and to what extent deficits exist in multiple domains after subarachnoid hemorrhage, including cognition, emotion and behavior, and to investigate whether brain damage can be detected in patients with subarachnoid hemorrhage. We aim to determine which early measures of cognition, emotion and behavior, and brain damage in the subacute stage play a role in long-term recovery after subarachnoid hemorrhage. Recovery is defined as functioning at a societal participation level, with a focus on resuming and maintaining work, leisure activities, and social relationships over the long term. METHODS: The ICONS study is an observational, prospective, single-center cohort study. The study includes patients with subarachnoid hemorrhage admitted to the Neurosurgery Unit of the University Medical Centre Groningen in the Netherlands. The inclusion criteria include diagnosis of an aneurysmal subarachnoid hemorrhage or an angiographically negative subarachnoid hemorrhage, sufficient ability in the Dutch language, and age older than 18 years. Patients will undergo neuropsychological assessment and magnetic resonance imaging 6 months after the subarachnoid hemorrhage. Furthermore, patients will be asked to fill in questionnaires on multiple psychosocial measures and undergo a structured interview at 6 months, 1 year, and 2 years after the subarachnoid hemorrhage. The primary outcome measure of the ICONS study is societal participation 1 year after the subarachnoid hemorrhage, measured with the Dutch version of the Impact on Participation and Autonomy questionnaire. RESULTS: The study was launched in December 2019 and recruitment is expected to continue until June 2023. At the time of the acceptance of this paper, 76 patients and 69 healthy controls have been included. The first results are expected in early 2023. CONCLUSIONS: The ICONS study is the first to collect and combine data after subarachnoid hemorrhage in a variety of domains, including cognition, emotion and behavior, and brain damage. The results will contribute to a more comprehensive understanding of the consequences of both aneurysmal subarachnoid hemorrhage and angiographically negative subarachnoid hemorrhage, which may ultimately optimize timely treatment for this patient group by setting realistic and attainable goals to improve daily functioning. TRIAL REGISTRATION: Netherlands Trial Register NL7803; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7803. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38190.

EARL compliance and imaging optimisation on the Biograph Vision Quadra PET/CT using phantom and clinical data.

PURPOSE: Current European Association of Nuclear Medicine (EANM) Research Ltd. (EARL) guidelines for the standardisation of PET imaging developed for conventional systems have not yet been adjusted for long axial field-of-view (LAFOV) systems. In order to use the LAFOV Siemens Biograph Vision Quadra PET/CT (Siemens Healthineers, Knoxville, TN, USA) in multicentre research and harmonised clinical use, compliance to EARL specifications for 18F-FDG tumour imaging was explored in the current study. Additional tests at various locations throughout the LAFOV and the use of shorter scan durations were included. Furthermore, clinical data were collected to further explore and validate the effects of reducing scan duration on semi-quantitative PET image biomarker accuracy and precision when using EARL-compliant reconstruction settings. METHODS: EARL compliance phantom measurements were performed using the NEMA image quality phantom both in the centre and at various locations throughout the LAFOV. PET data (maximum ring difference (MRD) = 85) were reconstructed using various reconstruction parameters and reprocessed to obtain images at shorter scan durations. Maximum, mean and peak activity concentration recovery coefficients (RC) were obtained for each sphere and compared to EARL standards specifications. Additionally, PET data (MRD = 85) of 10 oncological patients were acquired and reconstructed using various reconstruction settings and reprocessed from 10 min listmode acquisition into shorter scan durations. Per dataset, SUVs were derived from tumour lesions and healthy tissues. ANOVA repeated measures were performed to explore differences in lesion SUVmax and SUVpeak. Wilcoxon signed-rank tests were performed to evaluate differences in background SUVpeak and SUVmean between scan durations. The coefficient of variation (COV) was calculated to characterise noise. RESULTS: Phantom measurements showed EARL compliance for all positions throughout the LAFOV for all scan durations. Regarding patient data, EARL-compliant images showed no clinically meaningful significant differences in lesion SUVmax and SUVpeak or background SUVmean and SUVpeak between scan durations. Here, COV only varied slightly. CONCLUSION: Images obtained using the Vision Quadra PET/CT comply with EARL specifications. Scan duration and/or activity administration can be reduced up to a factor tenfold without the interference of increased noise.

Effects of interventions on cerebral perfusion in the Alzheimer's disease spectrum: A systematic review.

Cerebral perfusion dysfunctions are seen in the early stages of Alzheimer's disease (AD). We systematically reviewed the literature to investigate the effect of pharmacological and non-pharmacological interventions on cerebral hemodynamics in randomized controlled trials involving AD patients or Mild Cognitive Impairment (MCI) due to AD. Studies involving other dementia types were excluded. Data was searched in April 2021 on MEDLINE, Embase, and Web of Science. Risk of bias was assessed using Cochrane Risk of Bias Tool. A meta-synthesis was performed separating results from MCI and AD studies. 31 studies were included and involved 310 MCI and 792 CE patients. The MCI studies (n = 8) included physical, cognitive, dietary, and pharmacological interventions. The AD studies (n = 23) included pharmacological, physical interventions, and phytotherapy. Cerebral perfusion was assessed with PET, ASL, Doppler, fNIRS, DSC-MRI, Xe-CT, and SPECT. Randomization and allocation concealment methods and subject characteristics such as AD-onset, education, and ethnicity were missing in several papers. Positive effects on hemodynamics were seen in 75 % of the MCI studies, and 52 % of the AD studies. Inserting cerebral perfusion outcome measures, together with established AD biomarkers, is fundamental to target all disease mechanisms and understand the role of cerebral perfusion in AD.

DeepStrain Evidence of Asymptomatic Left Ventricular Diastolic and Systolic Dysfunction in Young Adults With Cardiac Risk Factors.

Purpose: To evaluate if a fully-automatic deep learning method for myocardial strain analysis based on magnetic resonance imaging (MRI) cine images can detect asymptomatic dysfunction in young adults with cardiac risk factors. Methods: An automated workflow termed DeepStrain was implemented using two U-Net models for segmentation and motion tracking. DeepStrain was trained and tested using short-axis cine-MRI images from healthy subjects and patients with cardiac disease. Subsequently, subjects aged 18-45 years were prospectively recruited and classified among age- and gender-matched groups: risk factor group (RFG) 1 including overweight without hypertension or type 2 diabetes; RFG2 including hypertension without type 2 diabetes, regardless of overweight; RFG3 including type 2 diabetes, regardless of overweight or hypertension. Subjects underwent cardiac short-axis cine-MRI image acquisition. Differences in DeepStrain-based left ventricular global circumferential and radial strain and strain rate among groups were evaluated. Results: The cohort consisted of 119 participants: 30 controls, 39 in RFG1, 30 in RFG2, and 20 in RFG3. Despite comparable (>0.05) left-ventricular mass, volumes, and ejection fraction, all groups (RFG1, RFG2, RFG3) showed signs of asymptomatic left ventricular diastolic and systolic dysfunction, evidenced by lower circumferential early-diastolic strain rate (<0.05, <0.001, <0.01), and lower septal circumferential end-systolic strain (<0.001, <0.05, <0.001) compared with controls. Multivariate linear regression showed that body surface area correlated negatively with all strain measures (<0.01), and mean arterial pressure correlated negatively with early-diastolic strain rate (<0.01). Conclusion: DeepStrain fully-automatically provided evidence of asymptomatic left ventricular diastolic and systolic dysfunction in asymptomatic young adults with overweight, hypertension, and type 2 diabetes risk factors.

Cardiac Alterations on 3T MRI in Young Adults With Sedentary Lifestyle-Related Risk Factors.

Background: Young adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics for these cardiovascular risk factors. Methods: Non-athletic non-smoking asymptomatic adults aged 18-45 years were prospectively recruited and underwent 3Tesla cardiac MRI. Multivariate linear regression was performed to investigate independent associations of risk factor-related parameters with cardiac MRI values. Results: We included 311 adults (age, 32 ± 7 years; men, 49%). Of them, 220 subjects had one or multiple risk factors, while 91 subjects were free of risk factors. For overweight, increased body mass index (per SD = 5.3 kg/m2) was associated with increased left ventricular (LV) mass (+7.3 g), biventricular higher end-diastolic (LV, +8.6 ml), and stroke volumes (SV; +5.0 ml), higher native T1 (+7.3 ms), and lower extracellular volume (ECV, -0.38%), whereas the higher waist-hip ratio was associated with lower biventricular volumes. Regarding hypertension, increased systolic blood pressure (per SD = 14 mmHg) was associated with increased LV mass (+6.9 g), higher LV ejection fraction (EF; +1.0%), and lower ECV (-0.48%), whereas increased diastolic blood pressure was associated with lower LV EF. In T2D, increased HbA1c (per SD = 9.0 mmol/mol) was associated with increased LV mass (+2.2 g), higher right ventricular end-diastolic volume (+3.2 ml), and higher ECV (+0.27%). Increased heart rate was linked with decreased LV mass, lower biventricular volumes, and lower T2 values. Conclusions: Young asymptomatic adults with overweight, hypertension, and T2D show subclinical alterations in cardiac morphology, function, and tissue characteristics. These alterations should be considered in cardiac MRI-based clinical decision making.

Role of Brain Imaging in Drug Development for Psychiatry.

BACKGROUND: Over the last decades, many brain imaging studies have contributed to new insights in the pathogenesis of psychiatric disease. However, in spite of these developments, progress in the development of novel therapeutic drugs for prevalent psychiatric health conditions has been limited. OBJECTIVE: In this review, we discuss translational, diagnostic and methodological issues that have hampered drug development in CNS disorders with a particular focus on psychiatry. The role of preclinical models is critically reviewed and opportunities for brain imaging in early stages of drug development using PET and fMRI are discussed. The role of PET and fMRI in drug development is reviewed emphasizing the need to engage in collaborations between industry, academia and phase I units. RESULTS: Brain imaging technology has revolutionized the study of psychiatric illnesses, and during the last decade, neuroimaging has provided valuable insights at different levels of analysis and brain organization, such as effective connectivity (anatomical), functional connectivity patterns and neurochemical information that may support both preclinical and clinical drug development. CONCLUSION: Since there is no unifying pathophysiological theory of individual psychiatric syndromes and since many symptoms cut across diagnostic boundaries, a new theoretical framework has been proposed that may help in defining new targets for treatment and thus enhance drug development in CNS diseases. In addition, it is argued that new proposals for data-mining and mathematical modelling as well as freely available databanks for neural network and neurochemical models of rodents combined with revised psychiatric classification will lead to new validated targets for drug development.

Clinical relevance of the radiation dose bath in lower grade glioma, a cross-sectional pilot study on neurocognitive and radiological outcome.

Aim: To investigate the clinical relevance of the radiotherapy (RT) dose bath in patients treated for lower grade glioma (LGG). Methods: Patients (n = 17) treated with RT for LGG were assessed with neurocognitive function (NCF) tests and structural Magnetic Resonance Imaging (MRI) and categorized in subgroups based on tumour lateralisation. RT dose, volumetric results and cerebral microbleed (CMB) number were extracted for contralateral cerebrum, contralateral hippocampus, and cerebellum. The RT clinical target volume (CTV) was included in the analysis as a surrogate for focal tumour and other treatment effects. The relationships between RT dose, CTV, NCF and radiological outcome were analysed per subgroup. Results: The subgroup with left-sided tumours (n = 10) performed significantly lower on verbal tests. The RT dose to the right cerebrum, as well as CTV, were related to poorer performance on tests for processing speed, attention, and visuospatial abilities, and more CMB.In the subgroup with right-sided tumours (n = 7), RT dose in the left cerebrum was related to lower verbal memory performance, (immediate and delayed recall, r = -0.821, p = 0.023 and r = -0.937, p = 0.002, respectively), and RT dose to the left hippocampus was related to hippocampal volume (r = -0.857, p = 0.014), without correlation between CTV and NCF. Conclusion: By using a novel approach, we were able to investigate the clinical relevance of the RT dose bath in patients with LGG more specifically. We used combined MRI-derived and NCF outcome measures to assess radiation-induced brain damage, and observed potential RT effects on the left-sided brain resulting in lower verbal memory performance and hippocampus volume.

Postural and gait symptoms in de novo Parkinson's disease patients correlate with cholinergic white matter pathology.

INTRODUCTION: The postural instability gait difficulty motor subtype of patients with Parkinson's disease (PIGD-PD) has been associated with more severe cognitive pathology and a higher risk on dementia compared to the tremor-dominant subtype (TD-PD). Here, we investigated whether the microstructural integrity of the cholinergic projections from the nucleus basalis of Meynert (NBM) was different between these clinical subtypes. METHODS: Diffusion-weighted imaging data of 98 newly-diagnosed unmedicated PD patients (44 TD-PD and 54 PIGD-PD subjects) and 10 healthy controls, were analysed using diffusion tensor imaging, focusing on the white matter tracts associated with cholinergic projections from the NBM (NBM-WM) as the tract-of-interest. Quantitative tract-based and voxel-based analyses were performed using FA and MD as the estimates of white matter integrity. RESULTS: Voxel-based analyses indicated significantly lower FA in the frontal part of the medial and lateral NBM-WM tract of both hemispheres of PIGD-PD compared to TD-PD. Relative to healthy control, several clusters with significantly lower FA were observed in the frontolateral NBM-WM tract of both disease groups. Furthermore, significant correlations between the severity of the axial and gait impairment and NBM-WM FA and MD were found, which were partially mediated by NBM-WM state on subjects' attentional performance. CONCLUSIONS: The PIGD-PD subtype shows a loss of microstructural integrity of the NBM-WM tract, which suggests that a loss of cholinergic projections in this PD subtype already presents in de novo PD patients.