Noninvasive MRI Technique Research Articles

Blood Oxygen Level Dependent Magnetic Resonance Imaging Tissue Perfusion Protocol for Reliable Differentiation of Patients with Peripheral Artery Disease and Healthy Controls: Vascular Imaging

Introduction: While peripheral artery disease (PAD) is a clinical diagnosis, further characterisation of the ischaemic state is mainly based on imaging that delineates the arterial vasculature. There is currently no established imaging technique that directly quantifies the crucial pathophysiological process in PAD (i.e., tissue perfusion in the lower limb). Blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI) is a non-invasive functional MRI technique that allows for the quantification of skeletal muscle perfusion without the use of contrast agents.

Analytical and Numerical Connections between Fractional Fickian and Intravoxel Incoherent Motion Models of Diffusion MRI

Impaired tissue perfusion underlies many chronic disease states and aging. Diffusion-weighted imaging (DWI) is a noninvasive MRI technique that has been widely used to characterize tissue perfusion. Parametric models based on DWI measurements can characterize microvascular perfusion modulated by functional and microstructural alterations in the skeletal muscle. The intravoxel incoherent motion (IVIM) model uses a biexponential form to quantify the incoherent motion of water molecules in the microvasculature at low b-values of DWI measurements. The fractional Fickian diffusion (FFD) model is a parsimonious representation of anomalous superdiffusion that uses the stretched exponential form and can be used to quantify the microvascular volume of skeletal muscle. Both models are established measures of perfusion based on DWI, and the prognostic value of model parameters for identifying pathophysiological processes has been studied. Although the mathematical properties of individual models have been previously reported, quantitative connections between IVIM and FFD models have not been examined. This work provides a mathematical framework for obtaining a direct, one-way transformation of the parameters of the stretched exponential model to those of the biexponential model. Numerical simulations are implemented, and the results corroborate analytical results. Additionally, analysis of in vivo DWI measurements in skeletal muscle using both biexponential and stretched exponential models is shown and compared with analytical and numerical models. These results demonstrate the difficulty of model selection based on goodness of fit to experimental data. This analysis provides a framework for better interpreting and harmonizing perfusion parameters from experimental results using these two different models.

Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating.

Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.

Effect of Aging on the Viscoelastic Properties of Hippocampal Subfields Assessed with High-Resolution MR Elastography.

Age-related memory impairments have been linked to differences in structural brain parameters, including the integrity of the hippocampus (HC) and its distinct hippocampal subfields (HCsf). Imaging methods sensitive to the underlying tissue microstructure are valuable in characterizing age-related HCsf structural changes that may relate to cognitive function. Magnetic resonance elastography (MRE) is a noninvasive MRI technique that can quantify tissue viscoelasticity and may provide additional information about aging effects on HCsf health. Here, we report a high-resolution MRE protocol to quantify HCsf viscoelasticity through shear stiffness, μ, and damping ratio, ξ, which reflect the integrity of tissue composition and organization. HCsf exhibit distinct mechanical properties-the subiculum had the lowest μ and both subiculum and entorhinal cortex had the lowest ξ. Both measures correlated with age: HCsf μ was lower with age (P < 0.001) whereas ξ was higher (P = 0.002). The magnitude of age-related differences in ξ varied across HCsf (P = 0.011), suggesting differential patterns of brain aging. This study demonstrates the feasibility of using MRE to assess HCsf microstructural integrity and suggests incorporation of these metrics to evaluate HC health in neurocognitive disorders.

Evaluation of Sodium (23Na) MR-imaging as a Biomarker and Predictor for Neurodegenerative Changes in Patients With Alzheimer's Disease.

Sodium (23Na) MR imaging is a noninvasive MRI technique that has been shown to be sensitive to visualize biochemical information about tissue viability, their cell integrity, and cell function in various studies. The aim of this study was to evaluate differences in regional brain 23Na signal intensity between Alzheimer's disease (AD) and healthy controls to preliminarily evaluate the capability of 23Na imaging as a biomarker for AD. A total of 14 patients diagnosed with AD were included: 12 in the state of dementia and 2 with mild cognitive impairment (MCI), and 12 healthy controls (HC); they were all scanned on a 3T clinical scanner with a double tuned 1H/23Na birdcage head coil. After normalizing the signal intensity with that of the vitreous humor, relative tissue sodium concentration (rTSC) was measured after automated segmentation in the hippocampus, amygdala, basal ganglia, white matter (WM) and grey matter (GM) in both cerebral hemispheres. Patients with AD showed a significant increase in rTSC in comparison to healthy controls in the following brain regions: WM 13.6%; p=0.007, hippocampus 12.9%; p=0.003, amygdala 18.9%; p=0.0007. 23Na-MRI has the potential to be developed as a useful biomarker for the diagnosis of AD.

Crossed cerebellar diaschisis after stroke detected noninvasively by arterial spin-labeling MR imaging

BackgroundAs a noninvasive perfusion-weighted MRI technique, arterial spin-labeling (ASL) was becoming increasingly used to evaluate cerebral hemodynamics in many studies. The relation between ASL-MRI and crossed cerebellar diaschisis (CCD) was rarely discussed. In this study, the aim of our study was to assess the performance of ASL-MRI in the detection of crossed cerebellar diaschisis after stroke in compared with single-photon emission CT (SPECT).Results17 of 51(33.3%) patients revealed CCD phenomenon by the SPECT method. In CCD-positive group, CBFASL of ipsilateral cerebellar were significantly increased compared with contralateral cerebellar (p < 0.0001) while no significant differences (p = 0.063, > 0.001) in the CCD-negative group. Positive correlation was detected between admission National institute of health stroke scale (NIHSS) and asymmetry index of SPECT (AISPECT) (r = 0.351, p = 0.011), AIASL (r = 0.372, p = 0.007); infract volume and AISPECT (r = 0.443, p = 0.001), AIASL (r = 0.426, p = 0.002). Significant correlation was also found between cerebral blood flow of SPECT (CBFSPECT) and CBFASL, AISPECT and AIASL (r = 0.204, p = 0.04; r = 0.467, p = 0.001, respectively). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AIASL was 0.829.ConclusionsCBF derived from ASL-MRI could be valuable for assessment of CCD in supratentorial stroke patients. Additionally, CCD was significantly associated with larger ischemic volume and higher initial NIHSS score.

Increased blood-brain barrier permeability to water in the aging brain detected using noninvasive multi-TE ASL MRI.

PurposeA fundamental goal in the drive to understand and find better treatments for dementia is the identification of the factors that render the aging brain vulnerable to neurodegenerative disease. Recent evidence indicates the integrity of the blood–brain barrier (BBB) to be an important component of functional failure underlying age‐related cognitive decline. Practical and sensitive measurement is necessary, therefore, to support diagnostic and therapeutic strategies targeted at maintaining BBB integrity in aging patients. Here, we investigated changes in BBB permeability to endogenous blood water in the aging brain.MethodsA multiple‐echo‐time arterial spin‐labeling MRI technique, implemented on a 9.4T Bruker imaging system, was applied to 7‐ and 27‐month‐old mice to measure changes in water permeability across the BBB with aging.ResultsWe observed that BBB water permeability was 32% faster in aged mice. This occurred along with a 2.1‐fold increase in mRNA expression of aquaporin‐4 water channels and a 7.1‐fold decrease in mRNA expression of α‐syntrophin protein, which anchors aquaporin‐4 to the BBB.ConclusionAge‐related changes to water permeability across the BBB can be captured using noninvasive noncontrast MRI techniques.

Diffusion weighted imaging in breast cancer - Can it be a noninvasive predictor of nuclear grade?

Background:DWI and ADC values are noninvasive MRI techniques, which provide quantitative information about tumor heterogeneity.Aim:To determine the minimum and mean ADC values in breast carcinoma and to correlate ADC values with various prognostic factors.Settings and Design:Prospective observational study.Materials and Methods:Fifty-five patients with biopsy-proven breast carcinoma were included in this study. MRI with DWI was performed with Siemens 3T Skyra scanner. ADC values were measured by placing regions of interest (ROIs) within the targeted lesions on ADC maps manually. The histopathological and immunohistochemical analysis of surgical specimen was done to determine the prognostic factors.Statistical Analysis:Students T test and ANOVA were used to study the difference in ADC between two groups. Pearson correlation coefficient was used to quantify the correlation between ADC values and prognostic factors.Results:Lower grade (grade I) breast carcinoma had a significantly high ADC value as compared to higher grade carcinoma (grade II and III). For differentiating Grade I tumors from grade II and III, a minimum ADC cut-off value was 0.79 × 10-3 mm2/sec (83% sensitivity and 84% specificity) and a mean ADC cut-off value was 0.82 × 10-3 mm2/sec (83% sensitivity and 71% specificity) was derived. There was no significant correlation between ADC and other prognostic factors.Conclusion:ADC values can be used to differentiate lower grade breast carcinoma (grade I) from higher grades (grade II and III). Minimum ADC values are more accurate in predicting the grade of the breast tumor than mean ADC value.

Quantification of ASL Perfusion MRI in MCI Patients Using Single-Post Labeling Delay Model-Fitting Approach

Purpose: Neuroimaging techniques hold many promises to detect Alzheimer Disease (AD) at early stages before clinical symptoms fully develop, suggesting decreased regional Cerebral Blood Flow (CBF). Perfusion deficiencies are present from very early clinical phases of AD, i.e. Mild Cognitive Impairment (MCI) and persist well into the latest stages, demonstrating a pattern of increased hypo-perfusion with the disease development. Accurate quantification such as quantification model and noise reduction method is necessary to achievement of good results in insufficient Post Labeling Delay (PLD) time. Materials and Methods: Arterial Spin Labeling (ASL) is a non-invasive MRI technique to extract brain regional CBF, which in recent years gained wide acceptance for its value in clinical and neuroscience applications. In the present work, 44 participants in 2 groups were imaged (normal control and MCI) using single-Post Label Delay (single-PLD) model-fitting ASL Perfusion at 1.5T. Images were de-noised with Independent Component Analysis (ICA) algorithm and then preprocessing such as motion correction, distortion correction, normalization, and tissue segmentation analyzed with SPM12. Calibration image that needed to calculate absolute perfusion was estimated from the data by fitting a curve to the control images in the dataset. Absolute CBF values were finally extracted from the kinetic model quantification. Results: Perfusion decreases in the right precuneus (28%), right inferior partial cortex (22%) and right middle frontal cortex (20%) cortex in MCI subjects. Conclusion: According to the results, ASL-MRI is able to calculate perfusion changes associated with MCI.

Using variable-rate selective excitation (VERSE) radiofrequency pulses to reduce power deposition in pulsed arterial spin labeling sequence at 7 Tesla.

Arterial spin labeling (ASL) is an established noninvasive MRI technique used for cerebral blood flow measurement, which generally suffers from a low signal-to-noise ratio (SNR). The use of ultra-high fields to enhance sensitivity inevitably results in an increase in TR because of specific absorption rate (SAR) constraints, causing inadequate sampling of hemodynamic response in functional MRI, and adversely affecting concurrent measurement such as blood oxygen level dependent. To address this problem, variable-rate selective excitation (VERSE) radiofrequency (RF) pulses were used. The conventional (sinc) selective RF pulses of the Q2TIPS block in the PICORE pulsed ASL (PASL) sequence used for blood saturation were replaced by their equivalent VERSE RF waveforms. Nine healthy volunteers were scanned using the conventional and VERSE PASL sequences on a head-only 7T scanner operating in parallel transmit mode. VERSE PASL sequence provides perfusion images similar to the conventional version, with comparable perfusion SNR (conventional, 3.33 ± 0.48; VERSE, 3.26 ± 0.55) and temporal SNR (conventional, 1.02 ± 0.20; VERSE, 1.05 ± 0.12) for TR = 3.5 seconds and 70 measurements. With shorter acquisition time (TR = 2.5 seconds), VERSE PASL sequence still provides similar results to those acquired using the conventional PASL sequence with longer TR = 3.5 seconds. The use of VERSE RF pulses in the Q2TIPS block of a PASL sequence allowed for the reduction of RF power deposition and, consequently, an increase in the temporal resolution and/or perfusion SNR.

Value of diffusion MR imaging in differentiation of recurrent head and neck malignancies from post treatment changes

PurposeRole of diffusion-weighted (DW) MR imaging in differentiating residual or recurrent neck malignancies from postoperative/post-radiation changes with histopathological correlation and comparison with PET-CT. Methods and materialsProspective observational study for a period of 1 year in 62 post-radiation/post-operative patients suspected to have residual/recurrent tumors of neck with lesion diameter more than 5 mm measured on MRI. ResultsMean ADC for recurrent/residual tumors: 1.008 ± 0.220 × 10−3 mm2/s - significantly lower than mean ADC value for post-treatment changes of 1.69 ± 0.40 × 10−3 mm2/s (p < 0.0001). The overall diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the qualitative assessment for the use of DWI in differentiating tumors recurrence from post-treatment changes were 96.6%, 96% and 83.3%, respectively. Upon quantitative analysis of the DW imaging data, a threshold ADC value of 1.3 × 10−3 mm2/s used for differentiating between post-treatment changes and recurrent cancers showed the highest combined sensitivity of 94%, specificity of 83.3%, accuracy of 93.6%, positive predictive value of 95.9%, and negative predictive value of 83.3%. ConclusionDW MRI is a promising non-invasive MRI technique used to differentiate recurrent/residual head and neck malignancies from posttreatment changes based on ADC values. DWI offers advantage as it has a short scanning time and can be safely added to standard MRI protocol with minimum patient discomfort. Complementary use of DWI and PET/CT imaging may increase diagnostic confidence for differentiating recurrent disease from radiation therapy-induced changes after 6–12 months in posttreatment cases.

In vivo tibiofemoral cartilage strain mapping under static mechanical loading using continuous GRASP-MRI.

Quantification of dynamic biomechanical strain in articular cartilage in vivo; in situ using noninvasive MRI techniques is desirable and may potentially be used to assess joint pathology. To demonstrate the use of static mechanical loading and continuous 3D-MRI acquisition of the human knee joint in vivo to measure the strain in the tibiofemoral articular cartilage. Prospective. Five healthy human volunteers (four women, one man; age 25.6 ± 1.7) underwent MRI at rest, under static mechanical loading condition, and during recovery. A field strength of 3T was used. The sequence used was 3D-continuous golden angle radial sparse parallel (GRASP) MRI and compressed sensing (CS) reconstruction. Tibiofemoral cartilage deformation maps under loading and during recovery were calculated using an optical flow algorithm. The corresponding Lagrangian strain was calculated in the articular cartilage. Range of displacement and strain in each subject, and the resulting mean and standard deviation, were calculated. During the loading condition, the cartilage displacement in the direction of loading ranged from a minimum of -673.6 ± 121.9 μm to a maximum of 726.5 ± 169.5 μm. Corresponding strain ranged from a minimum of -7.0 ± 4.2% to a maximum of 5.4 ± 1.6%. During the recovery condition, the cartilage displacement in the same direction reduced to a minimum of -613.0 ± 129.5 μm and a maximum of 555.7 ± 311.4 μm. The corresponding strain range reduced to a minimum of -1.6 ± 7.5% to a maximum of 4.2 ± 2.6%. This study shows the feasibility of using static mechanical loading with continuous GRASP-MRI acquisition to measure the strain in the articular cartilage. By measuring strain during the loading and recovery phases, dynamic strain information in the articular cartilage might be able to be investigated. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:426-434.

Progress of obsessive-compulsive disorder in diffusion tensor imaging

Diffusion tensor imaging (DTI), a noninvasive MRI technique for measuring the integrity and direction of white matter in the brain, is a promising method to explore the pathogenesis of obsessive compulsive disorder (OCD). At present, the etiological research of OCD suggests that, in addition to the classical cortical-striatum-thalamus-cortical (CSTC)circuit, the parietal lobe, temporal lobe, occipital lobe and other regions of the brain are also involved in the pathogenesis of OCD. White matter fibers are important structure of material information communication in various brain regions and affected by individual neurodevelopment. Therefore, it is very important to explore the characteristics of white matter fiber in the brain of patients with OCD by using diffusion tensor imaging technology clarifying its role in the occurrence of OCD. This paper reviews the studies on uncinate fasciculus, superior longitudinal fasciculus, corpus callosum in adult DTI studies and the progress of DTI studies on children and adolescents. Key words: Obsessive-compulsive disorder; Diffusion tensor imaging; Diffusion tractography

Non-invasive assessment of placental perfusion in vivo using arterial spin labeling (ASL) MRI: A preclinical study in rats

IntroductionNon-invasive assessment of placental perfusion is of great interest to characterize placental function in clinical practice. This article proposes a strictly non-invasive MRI technique using ASL to quantify placental blood flow in vivo. The aim of this study was to develop a fMRI tool to quantify placental blood flow (PBF) in rat, by using arterial spin labeling (ASL) MRI at 4.7 T. Materials and methodsMRI was performed with a dedicated magnet for small animals, in pregnant rats on day 20 of the 22-day gestation period. A Look-Locker flow-sensitive alternating inversion recovery gradient echo sequence was developed as ASL technique (TE: 1.55 ms; TR: 3.5 ms, TI: 56 ms, deltaTI: 56 ms, FA: 20°, Matrix: 128 × 128, 8 segments, 4 Nex). Labeling was performed with global and slice-selective inversions, and T1 map was obtained for each mode of inversion. PBF was then derived from a compartmental model of the variation of T1 between global and slice-selective inversions. ResultsThe full protocol was completed and ASL image post-processing was successful in 18 rats. Forty-seven placentas were analyzed, with a mean PBF of 147 ± 70 ml/min/100 g of placenta, consistent with published values of placental perfusion using invasive techniques. ConclusionASL MRI is feasible for the quantification of PBF in rats at 4.7 T. This technique, which requires no administration of contrast media, could have implications for non-invasive longitudinal and in vivo animal studies and may be useful for the management of human pregnancies.

Mechanisms underlying effects of kiwifruit on intestinal function shown by MRI in healthy volunteers.

SummaryBackgroundChronic constipation affects approximately 17% of the population worldwide and remains an important unmet need since patients are often dissatisfied with treatment. Kiwifruit may offer an alternative to traditional laxatives and have been shown to increase stool volume, frequency and improve consistency.AimsUsing non‐invasive MRI techniques, we assessed the effect of ingestion of kiwifruit on fluid distribution in the intestines and bowel function.MethodsTwo period crossover trial of kiwifruit vs control in healthy adults. Intervention: two kiwifruits twice daily vs isocaloric control (maltodextrin) twice daily, consumed for a total of 3 days. Subjects underwent MRI scanning fasted and at hourly intervals for 7 hours on the third day. Primary outcome: T1 relaxation time of ascending colon (T1AC) using MRI. Secondary outcomes: Small bowel water content (SBWC), colonic volume, gut transit time, T1 of descending colon, stool frequency and form.ResultsFourteen volunteers completed the study. T1AC was higher after kiwifruit ingestion (P = 0.029) during the second half of the day (when meal residue would be expected to reach the AC, AUC T1 T240‐420 minutes; mean (SD) 137 (39) s*minute with kiwifruit versus 108 (40) s*minute with control. SBWC (P < 0.001), colon volumes (P = 0.004), as well as stool frequency (1.46 ± 0.66 with kiwifruit vs 1.14 ± 0.46 stools per day with control; P = 0.034) and stool form score (Bristol Stool Chart score 4.1 (0.9) with kiwifruit versus 3.4 (0.7) with control; P = 0.011) were markedly increased in participants consuming kiwifruit compared to control.ConclusionConsumption of kiwifruit in healthy volunteers increases water retention in the small bowel and ascending colon and increases total colonic volume. The data may explain the observed increase in stool frequency and looser stool consistencies, suggesting that kiwifruit could be used as a dietary alternative to laxatives in mild constipation.

Early functional connectivity deficits and progressive microstructural alterations in the TgF344-AD rat model of Alzheimer’s Disease: A longitudinal MRI study

The development and characterization of new improved animal models is pivotal in Alzheimer's Disease (AD) research, since valid models enable the identification of early pathological processes, which are often not accessible in patients, as well as subsequent target discovery and evaluation. The TgF344-AD rat model of AD, bearing mutant human amyloid precursor protein (APPswe) and Presenilin 1 (PSEN1ΔE9) genes, has been described to manifest the full spectrum of AD pathology similar to human AD, i.e. progressive cerebral amyloidosis, tauopathy, neuronal loss and age-dependent cognitive decline. Here, AD-related pathology in female TgF344-AD rats was examined longitudinally between 6 and 18 months by means of complementary translational MRI techniques: resting state functional MRI (rsfMRI) to evaluate functional connectivity (FC) and diffusion tensor imaging (DTI) to assess the microstructural integrity. Additionally, an evaluation of macroscopic changes (3D anatomical MRI) and an image-guided validation of ex vivo pathology were performed. We identified slightly decreased FC at 6 months followed by severe and widespread hypoconnectivity at 10 months of age as the earliest detectable pathological MRI hallmark. This initial effect was followed by age-dependent progressive microstructural deficits in parallel with age-dependent ex vivo AD pathology, without signs of macroscopic alterations such as hippocampal atrophy.This longitudinal MRI study in the TgF344-AD rat model of AD revealed early rsfMRI and DTI abnormalities as seen in human AD patients. The characterization of AD pathology in this rat model using non-invasive MRI techniques further highlights the translational value of this model, as well as its use for potential treatment evaluation.

S146. EFFECT OF CLOZAPINE ON REGIONAL CEREBRAL BLOOD FLOW IN TREATMENT-RESISTANT SCHIZOPHRENIA

BackgroundApproximately one-third of schizophrenia patients will not respond adequately to conventional antipsychotic treatment; termed treatment-resistant schizophrenia (TRS). The only antipsychotic recommended for this group is clozapine, which may have unique efficacy in improving residual symptoms. The biological mechanisms underlying its efficacy are poorly understood. Previous studies have examined the effects of clozapine on regional cerebral blood flow (rCBF) using radiotracer approaches in relatively small samples of patients, showing, in particular, frontal and limbic perfusion changes1,2,3. In this study, we evaluate the effects of clozapine on rCBF, measured with a non-invasive MRI technique - pulsed continuous arterial spin labelling (pCASL) - which does not require radiotracer injection, as part of an ongoing study to identify neuroimaging predictors and mediators of clozapine response.MethodsParticipants ≥18 years of age with TRS were recruited at the Institute of Psychiatry, Psychology & Neuroscience, Kings College London (UK). TRS status was ascertained by the documented failure to respond to at least two different antipsychotic trials of adequate length. Participants were either clozapine-naïve or had not taken clozapine for at least three months prior to the baseline MRI scan. After baseline MRI, clozapine was administered as part of routine clinical care for 12 weeks, after which a second MRI scan was performed. Symptomatic response was defined as a reduction of 20% of the Positive and Negative Syndrome Scale (PANSS)4 score and non-response was defined as <20% decrease in PANSS score.pCASL data was acquired on a General Electric 3 Tesla MR-750 MR scanner. Arterial blood was labelled using a long, adiabatic (1.8 seconds) radio frequency pulse. After a post-labelling delay of 2.025s, perfusion images were acquired with a 3D Fast Spin Echo spiral multi-shot readout (TE 32ms/TR = 5500ms; ETL = 64). Cerebral blood flow (CBF) maps were computed with a spatial resolution of 2x2x3mm, in a total acquisition time of less than 6min. CBF maps were pre-processed using the Automatic Software for ASL processing (ASAP) toolbox5. Changes in rCBF after 12 weeks of clozapine were analysed in a full factorial ANOVA design, using SPM 12 (www.fil.ion.ucl.ac.uk/spm). Clusters of significant CBF changes were assessed at p<0.05 after Family-Wise Error correction for cluster extent, using a cluster-forming threshold of T>2.74.ResultsThis is an interim analysis of 24 patients who completed both scans. Contrasts were examined at a whole brain, assumption-free voxel-wise analysis, restricted to grey matter and co-varied for global perfusion. Clozapine administration significantly decreased perfusion in the medial frontal gyrus. There was also a significant response x time interaction, centred in the left posterior cerebellum and extending to the bilateral visual cortex and right precuneus.DiscussionThese interim results indicate that pCASL may be able to identify brain regions in which activity is modulated by clozapine administration as well as areas that may mediate symptomatic improvement. A key question for future analyses will be the degree to which rCBF may predict symptomatic response to clozapine, as the ability to predict a good likelihood of response could enable earlier clozapine initiation.

Sildenafil Improves Vascular and Metabolic Function in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of degenerative dementia in the aging population. Patients with AD have alterations in cerebral hemodynamic function including reduced cerebral blood flow (CBF) and cerebral metabolic rate. Therefore, improved cerebrovascular function may be an attractive goal for pharmaceutical intervention in AD. We wished to observe the acute effects of sildenafil on cerebrovascular function and brain metabolism in patients with AD. We used several novel non-invasive MRI techniques to investigate the alterations of CBF, cerebral metabolic rate of oxygen (CMRO2), and cerebrovascular reactivity (CVR) after a single dose of sildenafil administration in order to assess its physiological effects in patients with AD. CBF, CMRO2, and CVR measurements using MRI were performed before and one hour after the oral administration of 50 mg sildenafil. Baseline Montreal Cognitive Assessment score was also obtained. Complete CBF and CMRO2 data were obtained in twelve patients. Complete CVR data were obtained in eight patients. Global CBF and CMRO2 significantly increased (p = 0.03, p = 0.05, respectively) following sildenafil administration. Voxel-wise analyses of CBF maps showed that increased CBF was most pronounced in the bilateral medial temporal lobes. CVR significantly decreased after administration of sildenafil. Our data suggest that a single dose of sildenafil improves cerebral hemodynamic function and increases cerebral oxygen metabolism in patients with AD.

Functional MRI for Surgery of Gliomas.

Advanced neuroimaging techniques such as functional MRI (fMRI) and diffusion MR tractography have been increasingly used at every stage of the surgical management of brain gliomas, as a means to improve tumor resection while preserving brain functions. This review provides an overview of the last advancements in the field of functional MRI techniques, with a particular focus on their current clinical use and reliability in the preoperative and intraoperative setting, as well as their future perspectives for personalized multimodal management of patients with gliomas. fMRI and diffusion MR tractography give relevant insights on the anatomo-functional organization of eloquent cortical areas and subcortical connections near or inside a tumor. Task-based fMRI and diffusion tensor imaging (DTI) tractography have proven to be valid and highly sensitive tools for localizing the distinct eloquent cortical and subcortical areas before surgery in glioma patients; they also show good accuracy when compared with intraoperative stimulation mapping data. Resting-state fMRI functional connectivity as well as new advanced HARDI (high angular resolution diffusion imaging) tractography methods are improving and reshaping the role of functional MRI for surgery of gliomas, with potential benefit for personalized treatment strategies. Noninvasive functional MRI techniques may offer the opportunity to perform a multimodal assessment in brain tumors, to be integrated with intraoperative mapping and clinical data for improving surgical management and oncological and functional outcome in patients affected by gliomas.

Using functional and molecular MRI techniques to detect neuroinflammation and neuroprotection after traumatic brain injury

This study was designed to investigate whether functional and molecular MRI techniques are sensitive biomarkers for assessment of neuroinflammation and drug efficacy after traumatic brain injury (TBI) in rats. We subjected rats to a controlled cortical impact model and used behavioral tests, histology, and immunofluorescence to assess whether flavonoid pinocembrin provides cerebral protection and improves functional recovery. Most importantly, we used multiple noninvasive structural, functional, and molecular MRI techniques to examine whether the pinocembrin-related neuroprotection and attenuation of neuroinflammation can be detected in vivo. Significant increases in cerebral blood flow (CBF) and amide proton transfer-weighted (APTw) MRI signals were observed in the perilesional areas in untreated TBI rats at 3days and could be attributed to increased glial response. In addition, increased apparent diffusion coefficient and decreased magnetization transfer ratio signals in untreated TBI rats over time were likely due to edema. Post-treatment with pinocembrin decreased microglial/macrophage activation at 3days, consistent with the recovery of CBF and APTw MRI signals in regions of secondary injury. These findings suggest that pinocembrin provides cerebral protection for TBI and that multiple MRI signals, CBF and APTw in particular, are sensitive biomarkers for identification and assessment of neuroinflammation and drug efficacy in the TBI model.