Arterial Spin Labeling Research Articles

NIMG-03. USE OF ARTERIAL SPIN LABELING TO DIFFERENTIATE ICTAL PHENOMENON FROM TUMOR PROGRESSION IN HIGH GRADE ASTROCYTOMA

Abstract A 39-year-old female with grade-3 left parietal IDH-mutant astrocytoma following resection presented with convulsive status. EEG showed electrographic seizures arising from the left parietal region. MRI-brain showed the left temporoparietal post-treatment bed without any contrast enhancement (Fig-1A). Arterial spin labeling (ASL) – MR perfusion showed markedly increased cerebral blood flow (CBF) in the left temporoparietal lobe (Fig-1 C, D) with corresponding diffusion restriction (Fig-1B). Repeat imaging two weeks after the seizure control showed complete resolution (Fig-2) suggesting the imaging abnormalities to be a peri-ictal phenomenon.1 ASL-MR perfusion is a highly sensitive marker of increased CBF with its emerging application in distinguishing tumor progression (increased CBF) from post-treatment changes such as radiation necrosis (reduced CBF).1,2 This case highlights the utility of ASL-MR perfusion in differentiating peri/post-ictal phenomenon (increased CBF without T1-contrast enhancement) from tumor progression (increased CBF with T1-contrast enhancement) when employed routinely in clinical oncology practice.

NIMG-84. BELZUTIFAN REDUCTION OF CEREBRAL BLOOD FLOW IN VHL-ASSOCIATED HEMANGIOBLASTOMA PREDICTS RESPONSE TO TREATMENT

Abstract Hemangioblastoma (HMB) is a vascular-origin tumor occurring primarily in the cerebellum. Treatment typically involves surgical resection of the solid part of the tumor or stereotactic radiosurgery. An emerging treatment for hemangioblastoma is belzutifan (BZF), a hypoxia-inducible factor 2a (HIF2a) inhibitor. A recent trial found BZF to control hemangioblastoma in patients with von Hippel Lindau (vHL) syndrome. Perfusion MRI techniques including arterial spin labelling (ASL) and can be used to determine relative cerebral blood flow (rCBF). No prior studies have investigated rCBF in hemangioblastoma with relation to belzutifan, and the mechanism of action of belzutifan on hemangioblastoma is not well understood. Here, we aim to measure the response in rCBF in patients with vHL-associated hemangioblastoma treated with belzutifan. This retrospective cohort study constituted a group of seven patients with vHL-associated hemangioblastoma treated with Belzutifan at a daily oral dose of 120mg. Perfusion MRI with ASL sequences were acquired as part of the tumor imaging protocol. We quantified rCBF of the tumors prior to treatment, following intiation of BZF, and at most recent follow-up. Statistics were performed using R studio. The long axis diameter, volume of the solid tumor, rCBF mean, rCBF max, N mean, N max of lesions all decreased after Belzutifan treatment (p<0.001). While the long axis diameter of the cyst in cystic lesions did not show statistically significant change, the volume of cysts decreased significantly on Belzutifan (p=0.016). Spearman’s rank correlation analysis demonstrated association between change in rCBF mean, rCBF max, N mean and N max to % reduction in tumor volume. In addition, change in rCBF mean, change in rCBF max and change in N max all showed statistically significant association on multiple linear regression. Finally, early change in CBF and N predicted further volumetric response to treatment with belzutifan. We demonstrate that vHL-associated hemangioblastoma demonstrates decrease in rCBF in conjunction with and predictive of decreased volume following treatment with belzutifan.

The influence of alterations in the composition of intestinal microbiota on neurovascular coupling and cognitive dysfunction in individuals afflicted with CSVD

IntroductionAn expanding body of research has explored the crucial role of gut microbiota in cerebral small vessel disease (CSVD). The objective of this study is to investigate alterations in the gut microbiota structure among CSVD patients, to explore the correlation between differential taxonomic levels and the neurovascular coupling index as well as cognitive function and to elucidate the imaging and biomarkers of mild cognitive impairment (MCI) in CSVD. MethodsWe enrolled 104 patients with CSVD and 40 healthy controls (HC). Based on cognitive test scores, CSVD patients were categorized into a cognitively normal group (CSVD-NCI, n=61) and a mild cognitive impairment group (CSVD-MCI, n=43). Performing magnetic resonance imaging (MRI) scans, gut microbiota analysis, as well as clinical and neuropsychological assessments for all participants. Based on arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging data, cerebral blood flow (CBF) and neural activity indices are computed. The coupling indices of CBF/mReHo, CBF/mfALFF, CBF/mALFF, and CBF/mDC are calculated to assess the whole-brain neurovascular coupling changes in patients with CSVD. ResultsSpecies annotation revealed differences in the composition at the phylum and genus levels among the HC, CSVD-NCI, and CSVD-MCI groups. Additionally, differential analysis using the Kruskal-Wallis test demonstrated specific dominant microbial communities in all three groups. The relative abundance of certain dominant microbial communities in CSVD patients exhibited correlations with neurovascular coupling and cognitive function. The combined assessment of Bacteroides genus and CBF/mDC proved effective in distinguishing between CSVD-NCI and CSVD-MCI, providing a novel non-invasive approach for the diagnosis of MCI in CSVD.

Sensitivity assessment of QSM+qBOLD (or QQ) in detecting elevated oxygen extraction fraction (OEF) in physiological change.

The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values. MRI data were obtained from 11 healthy subjects during resting state (RS) and hyperventilation state (HV) using a 3 T MRI with a three-dimensional multi-echo gradient echo sequence (mGRE) and arterial spin labeling (ASL). Region of interest (ROI) analysis and paired t-tests were used to compare OEF, CMRO2 and CBF between QQ and QSM. Similar to QSM, QQ showed higher OEF during HV compared to RS: in cortical gray matter, QQ-OEF and QSM-OEF was 36.44.7% and 35.312.5% at RS and 45.011.6% and 45.014.8% in HV, respectively. These findings demonstrate QQ's ability to detect physiological changes and suggest its potential in studying brain metabolism in neurological disorders.

Cerebral blood flow and arterial transit time responses to exercise training in older adults

Brain vascular health worsens with age, as is made evident by resting grey matter cerebral blood flow (CBFGM) reductions and lengthening arterial transit time (ATTGM). Exercise training can improve aspects of brain health in older adults, yet its effects on CBFGM and ATTGM remain unclear. This randomised controlled trial assessed responses of CBFGM and ATTGM to a 26 week exercise intervention in 65 healthy older adults (control: n = 33, exercise: n = 32, aged 60–81 years), including whether changes in CBFGM or ATTGM were associated with changes in cognitive functions. Multiple-delay pseudo-continuous arterial spin labelling data were used to estimate resting global and regional CBFGM and ATTGM. Results showed no between-group differences in CBFGM or ATTGM following the intervention. However, exercise participants with the greatest cardiorespiratory gains (n = 17; ∆V̇O2peak >2 mL/kg/min) experienced global CBFGM reductions (-4.0 [-7.3, -0.8] mL/100 g/min). Cognitive functions did not change in either group and changes were not associated with changes in CBFGM or ATTGM. Our findings indicate that exercise training in older adults may induce global CBFGM reductions when high cardiorespiratory fitness gains are induced, but this does not appear to affect cognitive functions.

Phosphaturic Mesenchymal Tumor and Tumor-Induced Osteomalacia: A Report of 5 Cases, Including 2 Skull Base Cases With Arterial Spin Label Perfusion.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired bone mineralization secondary to secretion of fibroblast growth factor 23 (FGF23) from mesenchymal tumors (phosphaturic mesenchymal tumors, PMTs). PMTs have wide anatomical distribution but typically affect extremities and craniofacial bones. Diagnosis of TIO/PMT is often delayed, and a high index of suspicion is essential in patients with unexplained fractures, but many physicians lack familiarity with TIO/PMT and simply attribute fractures to the more common diagnosis of osteoporosis. We present 5 cases of TIO, with 4 having long histories of multiple insufficiency fractures prior to recognition of TIO and localization of a PMT. Four patients were treated surgically, while 1 preferred medical management. Two patients had lesions localized to the skull base, both of which showed marked hypervascularity on arterial spin label perfusion imaging. Thus, arterial spin label may not only help to localize these tumors, but may also be a helpful supplemental imaging finding in supporting this diagnosis. PMT should be considered in the differential diagnosis for hypervascular skull base masses, especially if the patient has any history of insufficiency fracture or imaging evidence of osteopenia, as early diagnosis of TIO can help prevent disabling complications.

Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.

Non-invasive imaging modalities for diagnosing pulsatile tinnitus: a comprehensive review and recommended imaging algorithm.

Pulsatile tinnitus (PT) is a challenging diagnostic condition arising from various vascular, neoplastic, and systemic disorders. Non-invasive imaging is essential for identifying underlying causes while minimizing risks of invasive diagnostic angiography. Although no consensus exists on the primary imaging modality for PT and currently CT, ultrasound, and MRI are used in the diagnostic pathway, MRI is increasingly preferred as the first-line screening test for its diagnostic efficacy and safety. MRI protocols such as time-of-flight, magnetic resonance angiography, diffusion-weighted imaging, and arterial spin labeling can identify serious causes, including vascular shunting lesions, venous sinus stenosis, and tumors. In this narrative review of the current literature we discuss the benefits and limitations of various non-invasive imaging modalities in identifying the characteristic imaging findings of the most common causes of PT and also provide an algorithm that clinicians can use to guide the imaging evaluation.

Evaluation of radiation induced brain injury in nasopharyngeal carcinoma patients based on multi-parameter quantitative MRI: A prospective longitudinal study

PurposeThree dimensional pulsed continuous arterial spin labeling (3D-pCASL) and incoherent movement within voxels (IVIM) imaging was combined to assess dynamic microscopic structure changes of the hippocampus and temporal lobe white matter (TLWM) of nasopharyngeal carcinoma (NPC) patients post intensity-modulated radiation therapy (IMRT). MethodsForty-six patients who were first diagnosed with NPC and underwent IMRT were prospectively enrolled. 3D-CASL and IVIM were performed pre-RT, within 1 week (1 W) post-RT, 3 months (3 M) post-RT, 6 months (6 M) post-RT, and 18 months (18 M) post-RT. Twenty-seven patients completed follow-ups for all time periods, and their data were analyzed. The cerebral flow (CBF) derived from ASL, and apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (F) derived from IVIM of hippocampus and TLWM were analyzed. The quantitative parameters were measured before RT as the baseline, and the corresponding parameter values and change rates at each time point post-RT were compared using the non-parametric Wilcoxon rank sum test. ResultsAt 1 W post-RT, CBF showed a significant increase and peaked in both the hippocampus and TLWM (p < 0.05) with change rate of 30.3 % and 24.1 %. In the hippocampus, both D and D* were significantly increased from pre-RT to 6 M post-RT with change rate of 6.66 % and 34.7 %, while D*-values remained significantly higher than pre-RT at 12 months post-RT with change rate of 41.2 %. In the TLWM, the F firstly increased and then decreased, and was significantly decreased from pre-RT to 6 M post-RT with change rate of 20.2 %. Conclusion3D-PCASL and IVIM can indirectly reflecting the developmental pattern and molecular mechanism of RT induced brain injury.

Evaluation of arterial spin labeling in the diagnosis and monitoring of myelin oligodendrocyte glycoprotein-associated cerebral cortical encephalitis.

Myelin oligodendrocyte glycoprotein (MOG)-associated disorders are inflammatory demyelinating diseases of the CNS. Cerebral cortical encephalitis (CCE) is characterized by cortical fluid-attenuated inversion recovery hyperintensity with seizures and headaches. We report two cases of MOG antibody-associated CCE (MOG-CCE) evaluated using serial MRI sequences, including arterial spin labeling (ASL), pre- and posttreatment. In both patients, ASL demonstrated hyperperfusion correlating with disease activity, which normalized following steroid therapy. Our cases highlight the usefulness of ASL in early detection, monitoring, and assessment of treatment response in MOG-CCE.

Altered neurovascular coupling in semantic variant primary progressive aphasia

Background Semantic variant primary progressive aphasia (svPPA) is one of the main clinical phenotypes of frontotemporal lobar degeneration. Changes in both neuronal activity and cerebral perfusion have been observed in svPPA, suggesting a possible breakdown of neurovascular coupling (NVC). Objective To investigate alterations in NVC and their correlations with clinical manifestations in svPPA patients. Methods In this study, a cohort consisting of 19 subjects diagnosed with svPPA and 36 cognitively unimpaired controls (CUCs) have been enrolled for analysis. All participants underwent multimodal magnetic resonance imaging (MRI) scans, resting-state functional MRI and arterial spin labelling, and neuropsychological assessments. The amplitude of low-frequency fluctuations (ALFF) and cerebral blood flow (CBF) were obtained to measure neural activity and perfusion, respectively. The calculation of voxel CBF-ALFF correlation and CBF/ALFF ratio enables the assessment of global NVC and regional NVC, respectively. Correlations between the CBF/ALFF ratios and cognitive scores of the svPPA patients were analyzed. The relationships between the CBF/ALFF ratios and the cognitive performance of the svPPA patients were investigated through correlational analyses. Results Compared with CUCs, svPPA patients had decreased global CBF-ALFF correlation coefficients ( p &lt; 0.001) and lower CBF/ALFF ratios in bilateral inferior temporal gyrus, fusiform gyrus, left temporal pole and middle temporal gyrus ( p &lt; 0.05). In svPPA patients, the CBF/ALFF ratios in the left inferior and middle temporal gyrus correlated positively with naming ability and general cognition, respectively. Conclusions The study indicate that NVC is disrupted in svPPA patients and is relevant to cognitive and language function.

Sitting foot: posture dependent changes of volume, edema and perfusion of the foot. A prospective interventional study with 27 volunteers

BackgroundSitting is known to be bad for your cardiovascular health. We furthermore hypothesized that sitting posture will reduce perfusion of the foot and increase edema, possibly predisposing to disease like osteochondritis.MethodsWe included 27 healthy volunteers and performed MRI measurements including arterial spin labelling (ASL) and intravoxel incoherent motion (IVIM) perfusion as well as short tau inversion recovery (STIR) edema measurement and 3D volumetry. After randomization, the elevation of one foot during the day was used as an intervention.ResultsIntra- and interrater variability was 1–6%. ASL perfusion measurement was hindered by artifacts. IVIM perfusion showed no significant changes during supine measurements. Volumetry could demonstrate a highly significant (p = 0.00005) volume increase, while the intervention led to a significant (p = 0.0076) volume decrease during the day. However, the water content in STIR remained unchanged and the normalized (quotient bone/muscle) edema was reduced on the control side (p = 0.006) and increased on the intervention side (p = 0.01).ConclusionsSitting all day leads to swelling of the healthy foot. Compensation in healthy subjects seems to prevent lasting perfusion changes or edema evolution in the bone despite an increase of muscle signal and volume increase. Thus, the etiology of osteochondritis needs further studies.

Pharmacological manipulation of neurotransmitter activity induces disparate effects on cerebral blood flow and resting-state fluctuations

Abstract Functional MRI methods can assess aspects of drug-induced brain response. Resting blood oxygenation level dependent (BOLD) fMRI and arterial spin labeling (ASL) perfusion MRI indirectly measure brain function through the coupling of activity to cerebral blood flow (CBF) and oxygenation but their relative sensitivity has not been directly compared. We assessed changes in resting measures of BOLD and ASL MRI in response to two neurotransmitter modulators: citalopram, a selective serotonin reuptake inhibitor, and alprazolam, a positive allosteric modulator of GABA type A receptor. Thirty healthy subjects were imaged in a placebo-controlled study, with N=20 subjects receiving each treatment as part of an incomplete block design. Time-averaged CBF images from ASL and measures of resting-state fluctuations of BOLD and ASL images were assessed for significant effects. Following acute citalopram administration, analysis of the ASL data showed a reduction in time-averaged regional CBF in regions associated with high levels of 5-HT1A receptor density. In contrast, following alprazolam administration, BOLD amplitude of low frequency fluctuations showed a highly significant and cortically widespread increase, consistent with the distribution of GABA-A receptors. Only a marginal decrease in ASL CBF was detected after alprazolam intake. BOLD and ASL are each sensitive to drugs targeting neurotransmitter systems, but appear to reflect different aspects of neural metabolism and the balance between excitatory and inhibitory activity. Accordingly, their combination may best capture the effects of neurotransmitter modulations, and thus be advantageous for pharmacological MRI studies.

The Influence of Anthropometric Factors on Renal mpMRI: Insights From Regional Analysis.

Multiparametric MRI (mpMRI) provides detailed insights into renal function, but the impact of anthropometric factors on renal imaging is not fully understood. To investigate regional correlations between mpMRI parameters and age, body mass index (BMI), and body surface area (BSA). Prospective, cross-sectional observational study. Twenty-nine healthy volunteers (44.5 ± 18.3 years, 18 females) without a history of renal disease. 3-T, pseudo-continuous arterial spin labeling, multi-echo gradient-recalled echo, diffusion-weighted imaging, T1 and T2 mapping. Bilateral kidneys were segmented into nine concentric layers (outer cortex to inner regions) and nine equiangular sections (lower to upper pole). Key parameters (renal blood flow [RBF], , apparent diffusion coefficient [ADC], T1 and T2 maps) were correlated with age, BMI, and BSA. Differences in parameters between age and BMI groups were also evaluated. Spearman correlation, Mann-Whitney U test, and rank-biserial correlation coefficient for effect size. A P-value <0.05 was considered statistically significant. RBF correlated negatively with age in all regions and BMI in inner layers and lower pole. ADC negatively correlated with BMI (significance was not reached in layers 2, 7, 8; P-value = 0.06-0.12) and BSA in layers 1-7. T1 negatively correlated with age in inner regions and lower medial pole. Significant positive correlations were found between age and (outermost layer, upper pole), age and T2 (inner and cranial-caudal regions), as well as BMI and T2 (except upper pole; P-value = 0.06). Significant differences between age groups were observed for RBF (all regions), (outermost and second innermost layers, central lateral region), T1 (innermost layer), and T2 (upper medial pole). Between BMI groups, ADC (middle layers, upper medial pole) and T2 (outermost and inner layers, lower pole to lateral region) differed significantly. Intrarenal variance of mpMRI parameters correlated with age, BMI, and BSA. 4 TECHNICAL EFFICACY: Stage 1.

Trajectories and sex differences of brain structure, oxygenation and perfusion functions in normal aging

Background: Brain structure, oxygenation and perfusion are important factors in aging. Coupling between regional cerebral oxygen consumption and perfusion also reflects functions of neurovascular unit (NVU). Their trajectories and sex differences during normal aging important for clinical interpretation are still not well defined. In this study, we aim to investigate the relationship between brain structure, functions and age, and exam the sex disparities.Method: A total of 137 healthy subjects between 20∼69 years old were enrolled with conventional MRI, structural three-dimensional T1-weighted imaging (3D-T1WI), 3D multi-echo gradient echo sequence (3D-mGRE), and 3D pseudo-continuous arterial spin labeling (3D-pCASL). Oxygen extraction fraction (OEF) and cerebral blood flow (CBF) were respectively reconstructed from 3D-mGRE and 3D-pCASL images. Cerebral metabolic rate of oxygen (CMRO2) were calculated as follows: CMRO2=CBF·OEF·[H]a, [H]a=7.377 μmol/mL. Brains were segmented into global gray matter (GM), global white matter (WM), and 148 cortical subregions. OEF, CBF, CMRO2, and volumes of GM/WM relative to intracranial volumes (rel_GM/rel_WM) were compared between males and females. Generalized additive models were used to evaluate the aging trajectories of brain structure and functions. The coupling between OEF and CBF was analyzed by correlation analysis. P or PFDR < 0.05 was considered statistically significant.Results: Females had larger rel_GM, higher CMRO2 and CBF of GM/WM than males (P < 0.05). With control of sex, CBF of GM significantly declined between 20 and 32 years, CMRO2 of GM declined subsequently from 33 to 41 years and rel_GM decreased significantly at all ages (R2 = 0.27, P < 0.001; R2 = 0.17, P < 0.001; R2 = 0.52, P < 0.001). In subregion analysis, CBF declined dispersedly while CMRO2 declined widely across most subregions of the cortex during aging. Robust negative coupling between OEF and CBF was found in most of the subregions (r range = -0.12∼-0.48, PFDR < 0.05).Conclusion: The sex disparities, age trajectories of brain structure and functions as well as the coupling of NVU in healthy individuals provide insights into normal aging which are potential targets for study of pathological conditions.

Repeatability and Reproducibility of pseudo-Continuous Arterial Spin Labeling Measured Brain Perfusion in Healthy Volunteers and Glioblastoma Patients.

Arterial spin labeled (ASL) MRI has gained recognition as a quantitative perfusion imaging method for managing patients with brain tumors. Limited studies have so far investigated the reproducibility of ASL-derived perfusion in patients with brain tumors. This study aims to evaluate intrasession repeatability and intersession reproducibility of perfusion measurements using 3D pseudo-continuous ASL (pCASL) with Cartesian TSE (TSE-CASPR) in healthy volunteers (HV) and glioblastoma (GBM) patients at 3 Tesla and compare against 3D pCASL with GRASE. This prospective study (NCT03922984) was approved by the institutional review board and written informed consent was obtained from all subjects. HV underwent repeated pCASL evaluations 2-4 weeks apart between November 2021 and October 2022. GBM patients were recruited for longitudinal MRI from September 2019 to February 2023. Intrasession repeatability (HV and GBM) and intersession reproducibility (HV only) of pCASL were assessed using linear regression, Bland-Altman analyses, intraclass correlation coefficient (ICC) with 95% confidence interval (CI), and within-subject coefficients of variation (wsCV). Twenty HV (9 men, age: 25.1±1.7 years, range 23-30 years) and 21 GBM patients (15 men; age: 59.8±14.3 years, range 28-81 years) were enrolled. Within imaging session, 3D pCASL measured perfusion with TSE-CASPR and GRASE respectively achieved high R2 values (0.88-0.95; 0.93-0.96), minimal biases (-0.46 to 0.81; -0.08 to 0.35 mL/100g/min), high ICC [95% CI] (0.96-0.98 [0.94-0.98]; 0.96-0.98 [0.92-0.99]), and low wsCV (6.64%-9.07%; 5.20%-8.16%) in HV (N=20) and GBM patients (N=21). Across imaging session, 3D pCASL in HV (N=20) achieved high R2 values (0.71; 0.82), minimal biases (-1.2; -0.90 mL/100g/min), high ICC [95% CI] values (0.85 [0.81-0.89]; 0.90 [0.87-0.93]), and low wsCV values (13.82%; 9.98%). Our study demonstrated excellent intrasession repeatability of 3D pCASL measured cerebral perfusion in HV and GBM patients and good to excellent intersession reproducibility in HV. 3D pCASL with GRASE performed slightly better than 3D pCASL with TSE-CASPR in HV; however, in GBM patients, 3D pCASL with TSE-CASPR showed better performance in tumor regions with nearly twofold higher SNR. ASL measured perfusion could serve as a non-contrast quantitative imaging biomarker to facilitate the management of GBM patients. ASL = arterial spin labeling; pCASL = pseudo-continuous arterial spin labeling; GBM = glioblastoma; CBF = cerebral blood flow; CASPR = Cartesian acquisition with spiral profile reordering; GRASE = gradient and spin echo; NAGM = normal-appearing gray matter.

Integrating standard epilepsy protocol, ASL-perfusion, MP2RAGE/EDGE and the MELD-FCD classifier in the detection of subtle epileptogenic lesions: a 3 Tesla MRI pilot study.

Malformations of cortical development (MCDs) in children with focal epilepsy pose significant diagnostic challenges, and a precise radiological diagnosis is crucial for surgical planning. New MRI sequences and the use of artificial intelligence (AI) algorithms are considered very promising in this regard, yet studies evaluating the relative contribution of each diagnostic technique are lacking. The study was conducted using a dedicated "EPI-MCD MR protocol" with a 3 Tesla MRI scanner in patients with focal epilepsy and previously negative MRI. MRI sequences evaluated included 3D FLAIR, 3D T1 MPRAGE, T2 Turbo Spin Echo (TSE), 3D T1 MP2RAGE, and Arterial Spin Labelling (ASL). Two paediatric neuroradiologists scored each sequence for localisation and extension of the lesion. The MELD-FCD AI classifier's performance in identifying pathological findings was also assessed. We only included patients where a diagnosis of MCD was subsequently confirmed on histology and/or sEEG. The 3D FLAIR sequence showed the highest yield in detecting epileptogenic lesions, with 3D T1 MPRAGE, T2 TSE, and 3D T1 MP2RAGE sequences showing moderate to low yield. ASL was the least useful. The MELD-FCD classifier achieved a 69.2% true positive rate. In one case, MELD identified a subtle area of cortical dysplasia overlooked by the neuroradiologists, changing the management of the patient. The 3D FLAIR sequence is the most effective in the MRI-based diagnosis of subtle epileptogenic lesions, outperforming other sequences in localisation and extension. This pilot study emphasizes the importance of careful assessment of the value of additional sequences.

Senolytic therapy preserves blood-brain barrier integrity and promotes microglia homeostasis in a tauopathy model

Cellular senescence, characterized by expressing the cell cycle inhibitory proteins, is evident in driving age-related diseases. Senescent cells play a crucial role in the initiation and progression of tau-mediated pathology, suggesting that targeting cell senescence offers a therapeutic potential for treating tauopathy associated diseases. This study focuses on identifying non-invasive biomarkers and validating their responses to a well-characterized senolytic therapy combining dasatinib and quercetin (D + Q), in a widely used tauopathy mouse model, PS19. We employed human-translatable MRI measures, including water extraction with phase-contrast arterial spin tagging (WEPCAST) MRI, T2 relaxation under spin tagging (TRUST), longitudinally assessed brain physiology and high-resolution structural MRI evaluated the brain regional volumes in PS19 mice. Our data reveal increased BBB permeability, decreased oxygen extraction fraction, and brain atrophy in 9-month-old PS19 mice compared to their littermate controls. (D + Q) treatment effectively preserves BBB integrity, rescues cerebral oxygen hypometabolism, attenuates brain atrophy, and alleviates tau hyperphosphorylation in PS19 mice. Mechanistically, D + Q treatment induces a shift of microglia from a disease-associated to a homeostatic state, reducing a senescence-like microglial phenotype marked by increased p16/Ink4a. D + Q-treated PS19 mice exhibit enhanced cue-associated cognitive performance in the tracing fear conditioning test compared to the vehicle-treated littermates, implying improved cognitive function by D + Q treatment. Our results pave the way for application of senolytic treatment as well as these noninvasive MRI biomarkers in clinical trials in tauopathy associated neurological disorders.

A timeline study on vascular co-morbidity induced cerebral endothelial dysfunction assessed by perfusion MRI

Endothelial dysfunction is considered a key element in the early pathogenesis of neurodegenerative disorders. Dysfunction of the cerebral endothelial cells can result in dysregulation of cerebral perfusion and disruption of the Blood Brain Barrier (BBB), leading to brain damage, neurodegeneration and cognitive decline. It has been shown that the presence of modifiable risk factors exacerbates endothelial dysfunction. This study primarily aimed to identify which among various perfusion MRI methodologies could be effectively utilized to non-invasively identify early pathological alterations as a result of endothelial dysfunction. We compared these perfusion MRI measurements to invasive immunohistochemistry to detect early pathological alterations in the cerebral vasculature of a rat model of multiple cardiovascular co-morbidities (the ZSF1 Obese rat) at several stages of the cerebrovascular pathology. We observed cerebral hyperperfusion, expressed by increased Cerebral Blood Flow (CBF) and increased BBB permeability in the ZSF1 Obese rats, at an early stage of disease development. The increase in CBF observed with Arterial Spin Labeling (ASL) was lost during later stages of disease progression. These findings are in line with recent clinical findings in early stages of Alzheimer's disease (AD), that also show early increases in CBF.

Evaluation of an Image-based Classification Model to Identify Glioma Subtypes Using Arterial Spin Labeling Perfusion MRI On the Publicly Available UCSF Glioma Dataset.

Glioma is acomplex cancer comprising various subtypes and mutations, which may have different metabolic characteristics that can potentially be investigated and identified using perfusion imaging. Therefore, the aim of this work was to use radiomics and machine learning analysis of arterial spin labeling MRI data to automatically differentiate glioma subtypes and mutations. Atotal of 495 Arterial Spin Labeling (ASL) perfusion imaging datasets from the UCSF Glioma database were used in this study. These datasets were segmented to delineate the tumor volume and classified according to tumor grade, pathological diagnosis, and IDH status. Perfusion image data was obtained from a3T MRI scanner using pseudo-continuous ASL. High level texture features were extracted for each ASL dataset using PyRadiomics after tumor volume segmentation and then analyzed using amachine learning framework consisting of ReliefF feature ranking and logistic model tree classification algorithms. The results of the evaluation revealed balanced accuracies for the three endpoints ranging from 55.76% (SD = 4.28, 95% CI: 53.90-57.65) for the tumor grade using 25.4 ± 37.21 features, 62.53% (SD = 2.86, 95% CI: 61.27-63.78) for the mutation status with 23.3 ± 29.17 picked features, and 80.97% (SD = 1.83, 95% CI: 80.17-81.78) for the pathological diagnosis which used 47.3 ± 32.72 selected features. Radiomics and machine learning analysis of ASL perfusion data in glioma patients hold potential for aiding in the diagnosis and treatment of glioma, mainly for discerning glioblastoma from astrocytoma, while performance for tumor grading and mutation status appears limited.