Refining hemodynamic correction in in vivo wide-field fluorescent imaging through linear regression analysis.

Accurate interpretation of in vivo wide-field fluorescent imaging (WFFI) data requires precise separation of raw fluorescence signals into neural and hemodynamic components. The classical Beer-Lambert law-based approach, which uses concurrent 530-nm illumination to estimate relative changes in cerebral blood volume (CBV), fails to account for the scattering and reflection of 530-nm photons from non-neuronal components leading to biased estimates of CBV changes and subsequent misrepresentation of neural activity. This study introduces a novel linear regression approach designed to overcome this limitation. This correction provides a more reliable representation of CBV changes and neural activity in fluorescence data. Our method is validated across multiple datasets, demonstrating its superiority over the classical approach.

High relative cerebral blood volume is associated with good long term clinical outcomes in acute ischemic stroke: a retrospective cohort study.

BACKGROUND: Endovascular therapy for acute ischemic stroke has been shown to be highly effective in selected patients. However, the ideal criteria for patient selection are still debated. It is well known that collateral flow is an important factor, but the assessment is often subjective and time-consuming. Relative cerebral blood volume (rCBV) is a putative indicator of collateral capacity and can be quickly and easily determined by automated quantitative analysis. We investigated the relationship between rCBV of the affected region and clinical outcome in patients with acute ischemic stroke after endovascular therapy. METHODS: We conducted a retrospective study on consecutive patients between January 2017 and May 2019. Patients with acute ischemic stroke of the anterior circulation who underwent imaging including computed tomography perfusion and were treated with mechanical thrombectomy (MT) were eligible for inclusion. rCBV was calculated automatically with RAPID software by dividing the average cerebral blood volume (CBV) of the affected region (time-to-maximum (Tmax) > 6 s) by the CBV of the unaffected contralateral side. The primary outcome was determined by the modified Rankin Scale (mRS) after 90 days. Good clinical outcome was defined as mRS ≤ 2. We compared means, performed mono- and multivariate logistical regression and calculated a receiver operating characteristic (ROC)-analysis to determine the ideal cutoff value to predict clinical outcomes. RESULTS: 155 patients were enrolled in this study. 66 patients (42.58%) had good clinical outcomes. Higher rCBV was associated with good clinical outcome (p < 0.001), even after adjustment for the patients' status according to mRS and National Institute of Health Stroke Scale (NIHSS) age and Alberta stroke program early computed tomography score (ASPECTS) at baseline (p = 0.006). ROC-analysis revealed 0.650 (confidence interval: 0.616-0.778) as the optimal cutoff value. CONCLUSION: Higher rCBV at baseline is associated with good clinical long-term outcomes in patients with acute ischemic stroke treated by MT. In this study we provide the biggest collective so far that gives evidence that rCBV can be a valuable tool to identify patients who might benefit from MT and are able give a threshold to help to offer patients MT in borderline cases.

Enhanced parameter estimation in multiparametric arterial spin labeling using artificial neural networks.

PURPOSE: Multiparametric arterial spin labeling (MP-ASL) can quantify cerebral blood flow (CBF) and arterial cerebral blood volume (CBVa). However, its accuracy is compromised owing to its intrinsically low SNR, necessitating complex and time-consuming parameter estimation. Deep neural networks (DNNs) offer a solution to these limitations. Therefore, we aimed to develop simulation-based DNNs for MP-ASL and compared the performance of a supervised DNN (DNNSup), physics-informed unsupervised DNN (DNNUns), and the conventional lookup table method (LUT) using simulation and in vivo data. METHODS: MP-ASL was performed twice during resting state and once during the breath-holding task. First, the accuracy and noise immunity were evaluated in the first resting state. Second, CBF and CBVa values were statistically compared between the first resting state and the breath-holding task using the Wilcoxon signed-rank test and Cliff's delta. Finally, reproducibility of the two resting states was assessed. RESULTS: Simulation and first resting-state analyses demonstrated that DNNSup had higher accuracy, noise immunity, and a six-fold faster computation time than LUT. Furthermore, all methods detected task-induced CBF and CBVa elevations, with the effect size being larger with the DNNSup (CBF, p = 0.055, Δ = 0.286; CBVa, p = 0.008, Δ = 0.964) and DNNUns (CBF, p = 0.039, Δ = 0.286; CBVa, p = 0.008, Δ = 1.000) than that with LUT (CBF, p = 0.109, Δ = 0.214; CBVa, p = 0.008, Δ = 0.929). Moreover, all the methods exhibited comparable and satisfactory reproducibility. CONCLUSION: DNNSup outperforms DNNUns and LUT with respect to estimation performance and computation time.

Follow-up infarct volume on fluid attenuated inversion recovery (FLAIR) imaging in distal medium vessel occlusions: the role of cerebral blood volume index.

BACKGROUND: Distal medium vessel occlusions (DMVOs) contribute substantially to the incidence of acute ischemic strokes (AIS) and pose distinct challenges in clinical management and prognosis. Neuroimaging techniques, such as Fluid Attenuation Inversion Recovery (FLAIR) imaging and cerebral blood volume (CBV) index derived from perfusion imaging, have significantly improved our ability to assess the impact of strokes and predict their outcomes. The primary objective of this study was to investigate relationship between follow-up infarct volume (FIV) as assessed by FLAIR imaging in patients with DMVOs. METHODS: This prospectively collected, retrospective reviewed cohort study included patients from two comprehensive stroke centers within the Johns Hopkins Medical Enterprise, spanning August 2018-October 2022. The cohort consisted of adults with AIS attributable to DMVO. Detailed imaging analyses were conducted, encompassing non-contrast CT, CT angiography (CTA), CT perfusion (CTP), and FLAIR imaging. Univariable and multivariable linear regression models were employed to assess the association between different factors and FIV. RESULTS: The study included 79 patients with DMVO stroke with a median age of 69 years (IQR, 62-77 years), and 57% (n = 45) were female. There was a negative correlation between the CBV index and FIV in a univariable linear regression analysis (Beta = - 16; 95% CI, - 23 to - 8.3; p < 0.001) and a multivariable linear regression model (Beta = - 9.1 per 0.1 change; 95% CI, - 15 to - 2.7; p = 0.006). Diabetes was independently associated with larger FIV (Beta = 46; 95% CI, 16 to 75; p = 0.003). Additionally, a higher baseline ASPECTS was associated with lower FIV (Beta = - 30; 95% CI, - 41 to - 20; p < 0.001). CONCLUSION: Our findings underscore the CBV index as an independent association with FIV in DMVOs, which highlights the critical role of collateral circulation in determining stroke outcomes in this patient population. In addition, our study confirms a negative association of ASPECTS with FLAIR FIV and identifies diabetes as independent factor associated with larger FIV. These insights pave the way for further large-scale, prospective studies to corroborate these findings, thereby refining the strategies for stroke prognostication and management.

Deep Learning for Perfusion Cerebral Blood Flow (CBF) and Volume (CBV) Predictions and Diagnostics.

Dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) is a non-invasive imaging technique for hemodynamic measurements. Various perfusion parameters, such as cerebral blood volume (CBV) and cerebral blood flow (CBF), can be derived from DSC-MRP, hence this non-invasive imaging protocol is widely used clinically for the diagnosis and assessment of intracranial pathologies. Currently, most institutions use commercially available software to compute the perfusion parametric maps. However, these conventional methods often have limitations, such as being time-consuming and sensitive to user input, which can lead to inconsistent results; this highlights the need for a more robust and efficient approach like deep learning. Using the relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) perfusion maps generated by FDA-approved software, we trained a multistage deep learning model. The model, featuring a combination of a 1D convolutional neural network (CNN) and a 2D U-Net encoder-decoder network, processes each 4D MRP dataset by integrating temporal and spatial features of the brain for voxel-wise perfusion parameters prediction. An auxiliary model, with similar architecture, but trained with truncated datasets that had fewer time-points, was designed to explore the contribution of temporal features. Both qualitatively and quantitatively evaluated, deep learning-generated rCBV and rCBF maps showcased effective integration of temporal and spatial data, producing comprehensive predictions for the entire brain volume. Our deep learning model provides a robust and efficient approach for calculating perfusion parameters, demonstrating comparable performance to FDA-approved commercial software, and potentially mitigating the challenges inherent to traditional techniques.

Cerebral blood volume sensitive layer-fMRI in the human auditory cortex at 7T: Challenges and capabilities.

The development of ultra high field fMRI signal readout strategies and contrasts has led to the possibility of imaging the human brain in vivo and non-invasively at increasingly higher spatial resolutions of cortical layers and columns. One emergent layer-fMRI acquisition method with increasing popularity is the cerebral blood volume sensitive sequence named vascular space occupancy (VASO). This approach has been shown to be mostly sensitive to locally-specific changes of laminar microvasculature, without unwanted biases of trans-laminar draining veins. Until now, however, VASO has not been applied in the technically challenging cortical area of the auditory cortex. Here, we describe the main challenges we encountered when developing a VASO protocol for auditory neuroscientific applications and the solutions we have adopted. With the resulting protocol, we present preliminary results of laminar responses to sounds and as a proof of concept for future investigations, we map the topographic representation of frequency preference (tonotopy) in the auditory cortex.

Whole-brain 3D mapping of oxygen metabolism using constrained quantitative BOLD.

Quantitative BOLD (qBOLD) MRI permits noninvasive evaluation of hemodynamic and metabolic states of the brain by quantifying parametric maps of deoxygenated blood volume (DBV) and hemoglobin oxygen saturation level of venous blood (Yv), and along with a measurement of cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2). The method, thus should have potential to provide important information on many neurological disorders as well as normal cerebral physiology. One major challenge in qBOLD is to separate deoxyhemoglobin's contribution to R2' from other sources modulating the voxel signal, for instance, R2, R2' from non-heme iron (R'2,nh), and macroscopic magnetic field variations. Further, even with successful separation of the several confounders, it is still challenging to extract DBV and Yv from the heme-originated R2' because of limited sensitivity of the qBOLD model. These issues, which have not been fully addressed in currently practiced qBOLD methods, have so far precluded 3D whole-brain implementation of qBOLD. Thus, the purpose of this work was to develop a new 3D MRI oximetry technique that enables robust qBOLD parameter mapping across the entire brain. To achieve this goal, we employed a rapid, R2'-sensitive, steady-state 3D pulse sequence (termed 'AUSFIDE') for data acquisition, and implemented a prior-constrained qBOLD processing pipeline that exploits a plurality of preliminary parameters obtained via AUSFIDE, along with additionally measured cerebral venous blood volume. Numerical simulations and in vivo studies at 3 T were performed to evaluate the performance of the proposed, constrained qBOLD mapping in comparison to the parent qBOLD method. Measured parameters (Yv, DBV, R'2,nh, nonblood magnetic susceptibility) in ten healthy subjects demonstrate the expected contrast across brain territories, while yielding group-averages of 64.0 ± 2.3 % and 62.2 ± 3.1 % for Yv and 2.8 ± 0.5 % and 1.8 ± 0.4 % for DBV in cortical gray and white matter, respectively. Given the Yv measurements, additionally quantified CBF in seven of the ten study subjects enabled whole-brain 3D CMRO2 mapping, yielding group averages of 134.2 ± 21.1 and 79.4 ± 12.6 µmol/100 g/min for cortical gray and white matter, in good agreement with literature values. The results suggest feasibility of the proposed method as a practical and reliable means for measuring neurometabolic parameters over an extended brain coverage.

Effect and safety of acupuncture on cerebrovascular reserve in patients with acute cerebral infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: As far as we know, no evidence has been established to assess the effects of acupuncture for acute cerebral infarction patients. Therefore, this systematic review and meta-analysis will be conducted to assess the efficacy and safety of acupuncture on cerebrovascular reserve in patients with acute cerebral infarction. METHODS: On June 20, 2021, the authors will perform a preliminary search in the PubMed, Embase, and Scopus databases using the following keywords: "acupuncture," "acute cerebral infarction." We will also examine the Clinical Trials Registry for other ongoing and unpublished studies. The inclusion criteria included (1) patients with acute cerebral infarction, (2) patients who received acupuncture, and (3) studies assessed cerebrovascular reserve, breath-holding index, Barthel index, and adverse events. All English language randomized controlled trials published within the last 20 years were eligible for inclusion. Primary outcome measures in our study are cerebrovascular reserve, and secondary outcome measures include the breath-holding index, Barthel index, and adverse events. All outcomes are pooled on a random-effect model. RESULTS: The results of this research will be delivered in a peer-reviewed journal. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/7M4BK.

Validating layer-specific VASO across species.

Cerebral blood volume (CBV) has been shown to be a robust and important physiological parameter for quantitative interpretation of functional (f)MRI, capable of delivering highly localized mapping of neural activity. Indeed, with recent advances in ultra-high-field (≥7T) MRI hardware and associated sequence libraries, it has become possible to capture non-invasive CBV weighted fMRI signals across cortical layers. One of the most widely used approaches to achieve this (in humans) is through vascular-space-occupancy (VASO) fMRI. Unfortunately, the exact contrast mechanisms of layer-dependent VASO fMRI have not been validated for human fMRI and thus interpretation of such data is confounded. Here we validate the signal source of layer-dependent SS-SI VASO fMRI using multi-modal imaging in a rat model in response to neuronal activation (somatosensory cortex) and respiratory challenge (hypercapnia). In particular VASO derived CBV measures are directly compared to concurrent measures of total haemoglobin changes from high resolution intrinsic optical imaging spectroscopy (OIS). Quantified cortical layer profiling is demonstrated to be in agreement between VASO and contrast enhanced fMRI (using monocrystalline iron oxide nanoparticles, MION). Responses show high spatial localisation to layers of cortical processing independent of confounding large draining veins which can hamper BOLD fMRI studies, (depending on slice positioning). Thus, a cross species comparison is enabled using VASO as a common measure. We find increased VASO based CBV reactivity (3.1 ± 1.2 fold increase) in humans compared to rats. Together, our findings confirm that the VASO contrast is indeed a reliable estimate of layer-specific CBV changes. This validation study increases the neuronal interpretability of human layer-dependent VASO fMRI as an appropriate method in neuroscience application studies, in which the presence of large draining intracortical and pial veins limits neuroscientific inference with BOLD fMRI.

Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and 18F-FMISO PET.

Tumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and 18F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and 18F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (rs = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (rs = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.

Integrated PET/MRI scanner with oxygen-15 labeled gases for quantification of cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen.

OBJECTIVES: Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) by PET with oxygen-15 labeled gases is useful for diagnosis and treatment planning in cases of chronic occlusive cerebrovascular disease. In the present study, CBF, CBV, OEF and CMRO2 were measured using the integrated design of PET/MRI scanner system. This is a first attempt to measure cerebral perfusion and oxygen metabolism using PET/MRI with oxygen-15 labeled gases. METHODS: PET/MRI measurements with the steady-state method of oxygen-15 labeled gases, carbon monoxide (C15O), oxygen (15O2), and carbon dioxide (C15O2) were performed on nine healthy men. Two kinds of attenuation correction for PET were performed using MRI with Dixon sequence (DIXON) and Dixon sequence with model-based bone segmentation (DIXONbone). A real-time motion correction of PET images was also performed using simultaneously measured MR images to detect head motion. RESULTS: Mean and SD values of CBF, CBV, OEF, and CMRO2 in the cerebral cortices with attenuation correction by DIXON were 31 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.5 ± 0.3 mL/100 mL/min without real-time motion correction, and 33 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.6 ± 0.3 mL/100 mL/min with real-time motion correction, respectively. Values with of CBF, CBV, OEF, and CMRO2 with attenuation correction by DIXONbone were 35 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.8 ± 0.3 mL/100 mL/min without real-time motion correction, and 38 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 3.0 ± 0.4 mL/100 mL/min with real-time motion correction, respectively. CONCLUSIONS: Using PET/MRI with oxygen-15 labeled gases, CBF, CBV, OEF, and CMRO2 could be measured. Values of CBF, CBV, and CMRO2 measured with attenuation correction by DIXON were significantly lower than those measured with correction by DIXONbone. One of the reasons for this is that attenuation correction of DIXON does not take into consideration of the photon absorption by bone. OEF values, corresponding to ratios of CMRO2 to CBF, were not affected by attenuation correction methods. Values of CBF and CMRO2 with a real-time motion correction were significantly higher than those without correction. Using PET/MRI with adequate corrections, similar values of CBF, CBV, OEF, and CMRO2 as PET alone scanner system reported previously were obtained. TRAIL REGISTRATION: The UMIN clinical trial number: UMIN000033382.

Comparison of Genetic Profiles and Prognosis of High-Grade Gliomas Using Quantitative and Qualitative MRI Features: A Focus on G3 Gliomas.

OBJECTIVE: To evaluate the association of MRI features with the major genomic profiles and prognosis of World Health Organization grade III (G3) gliomas compared with those of glioblastomas (GBMs). MATERIALS AND METHODS: We enrolled 76 G3 glioma and 155 GBM patients with pathologically confirmed disease who had pretreatment brain MRI and major genetic information of tumors. Qualitative and quantitative imaging features, including volumetrics and histogram parameters, such as normalized cerebral blood volume (nCBV), cerebral blood flow (nCBF), and apparent diffusion coefficient (nADC) were evaluated. The G3 gliomas were divided into three groups for the analysis: with this isocitrate dehydrogenase (IDH)-mutation, IDH mutation and a chromosome arm 1p/19q-codeleted (IDHmut1p/19qdel), IDH mutation, 1p/19q-nondeleted (IDHmut1p/19qnondel), and IDH wildtype (IDHwt). A prediction model for the genetic profiles of G3 gliomas was developed and validated on a separate cohort. Both the quantitative and qualitative imaging parameters and progression-free survival (PFS) of G3 gliomas were compared and survival analysis was performed. Moreover, the imaging parameters and PFS between IDHwt G3 gliomas and GBMs were compared. RESULTS: IDHmut G3 gliomas showed a larger volume (p = 0.017), lower nCBF (p = 0.048), and higher nADC (p = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV (p = 0.024) and lower nADC (p = 0.002) than IDHmut1p/19qnondel G3 gliomas. Moreover, IDHmut1p/19qdel tumors had the best prognosis and IDHwt tumors had the worst prognosis among G3 gliomas (p < 0.001). PFS was significantly associated with the 95th percentile values of nCBV and nCBF in G3 gliomas. There was no significant difference in neither PFS nor imaging features between IDHwt G3 gliomas and IDHwt GBMs. CONCLUSION: We found significant differences in MRI features, including volumetrics, CBV, and ADC, in G3 gliomas, according to IDH mutation and 1p/19q codeletion status, which can be utilized for the prediction of genomic profiles and the prognosis of G3 glioma patients. The MRI signatures and prognosis of IDHwt G3 gliomas tend to follow those of IDHwt GBMs.

Evolution of the stroke paradigm: A review of delayed recanalization.

While the time window for reperfusion after ischemic stroke continues to increase, many patients are not candidates for reperfusion under current guidelines that allow for reperfusion within 24 h after last known well time; however, many case studies report favorable outcomes beyond 24 h after symptom onset for both spontaneous and medically induced recanalization. Furthermore, modern imaging allows for identification of penumbra at extended time points, and reperfusion risk factors and complications are becoming better understood. Taken together, continued urgency exists to better understand the pathophysiologic mechanisms and ideal setting of delayed recanalization beyond 24 h after onset of ischemia.

Adaptive modulation of brain hemodynamics across stereotyped running episodes.

During locomotion, theta and gamma rhythms are essential to ensure timely communication between brain structures. However, their metabolic cost and contribution to neuroimaging signals remain elusive. To finely characterize neurovascular interactions during locomotion, we simultaneously recorded mesoscale brain hemodynamics using functional ultrasound (fUS) and local field potentials (LFP) in numerous brain structures of freely-running overtrained rats. Locomotion events were reliably followed by a surge in blood flow in a sequence involving the retrosplenial cortex, dorsal thalamus, dentate gyrus and CA regions successively, with delays ranging from 0.8 to 1.6 seconds after peak speed. Conversely, primary motor cortex was suppressed and subsequently recruited during reward uptake. Surprisingly, brain hemodynamics were strongly modulated across trials within the same recording session; cortical blood flow sharply decreased after 10-20 runs, while hippocampal responses strongly and linearly increased, particularly in the CA regions. This effect occurred while running speed and theta activity remained constant and was accompanied by an increase in the power of hippocampal, but not cortical, high-frequency oscillations (100-150 Hz). Our findings reveal distinct vascular subnetworks modulated across fast and slow timescales and suggest strong hemodynamic adaptation, despite the repetition of a stereotyped behavior.

Elevated glucose is associated with hemorrhagic transformation after mechanical thrombectomy in acute ischemic stroke patients with severe pretreatment hypoperfusion.

Several pretreatment variables such as elevated glucose and hypoperfusion severity are related to brain hemorrhage after endovascular treatment of acute stroke. We evaluated whether elevated glucose and severe hypoperfusion have synergistic effects in the promotion of parenchymal hemorrhage (PH) after mechanical thrombectomy (MT). We included 258 patients MT-treated who had a pretreatment computed tomography perfusion (CTP) and a post-treatment follow-up MRI. Severe hypoperfusion was defined as regions with cerebral blood volume (CBV) values < 2.5% of normal brain [very-low CBV (VLCBV)-regions]. Median baseline glucose levels were 119 (IQR = 105-141) mg/dL. Thirty-nine (15%) patients had pretreatment VLCBV-regions, and 42 (16%) developed a PH after MT. In adjusted models, pretreatment glucose levels interacted significantly with VLCBV on the prediction of PH (p-interaction = 0.011). In patients with VLCBV-regions, higher glucose was significantly associated with PH (adjusted-OR = 3.15; 95% CI = 1.08-9.19, p = 0.036), whereas this association was not significant in patients without VLCBV-regions. CBV values measured at pretreatment CTP in coregistered regions that developed PH or infarct at follow-up were not correlated with pretreatment glucose levels, thus suggesting the existence of alternative deleterious mechanisms other than direct glucose-driven hemodynamic impairments. Overall, these results suggest that both severe hypoperfusion and glucose levels should be considered in the evaluation of adjunctive neuroprotective strategies.

Oxygen extraction fraction mapping with multi-parametric quantitative BOLD MRI: Reduced transverse relaxation bias using 3D-GraSE imaging.

Magnetic resonance imaging (MRI)-based quantification of the blood-oxygenation-level-dependent (BOLD) effect allows oxygen extraction fraction (OEF) mapping. The multi-parametric quantitative BOLD (mq-BOLD) technique facilitates relative OEF (rOEF) measurements with whole brain coverage in clinically applicable scan times. Mq-BOLD requires three separate scans of cerebral blood volume and transverse relaxation rates measured by gradient-echo (1/T2∗) and spin-echo (1/T2). Although the current method is of clinical merit in patients with stroke, glioma and internal carotid artery stenosis (ICAS), there are relaxation measurement artefacts that impede the sensitivity of mq-BOLD and artificially elevate reported rOEF values. We posited that T2-related biases caused by slice refocusing imperfections during rapid 2D-GraSE (Gradient and Spin Echo) imaging can be reduced by applying 3D-GraSE imaging sequences, because the latter requires no slice selective pulses. The removal of T2-related biases would decrease overestimated rOEF values measured by mq-BOLD. We characterized effects of T2-related bias in mq-BOLD by comparing the initially employed 2D-GraSE and two proposed 3D-GraSE sequences to multiple single spin-echo reference measurements, both in vitro and in vivo. A phantom and 25 participants, including young and elderly healthy controls as well as ICAS-patients, were scanned. We additionally proposed a procedure to reliably identify and exclude artefact affected voxels. In the phantom, 3D-GraSE derived T2 values had 57% lower deviation from the reference. For in vivo scans, the formerly overestimated rOEF was reduced by -27% (p â€‹< â€‹0.001). We obtained rOEF â€‹= â€‹0.51, which is much closer to literature values from positron emission tomography (PET) measurements. Furthermore, increased sensitivity to a focal rOEF elevation in an ICAS-patient was demonstrated. In summary, the application of 3D-GraSE improves the mq-BOLD-based rOEF quantification while maintaining clinically feasible scan times. Thus, mq-BOLD with non-slice selective T2 imaging is highly promising to improve clinical diagnostics of cerebrovascular diseases such as ICAS.

FAP-specific PET signaling shows a moderately positive correlation with relative CBV and no correlation with ADC in 13 IDH wildtype glioblastomas.

OBJECTIVES: Targeting Fibroblast Activation Protein (FAP) is a new approach for glioblastoma imaging. In a recent pilot study glioblastomas showed elevated tracer uptake with high intratumoral heterogeneity in projection on the corresponding T2w/FLAIR and contrast enhanced MRI lesions. In this study, we correlated FAP-specific signaling with apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) signals in MRI to further characterize the significance of FAP uptake. METHODS: Clinical PET/CT scans of 13 glioblastoma patients were performed post i. v. administration of 68Ga-labelled-FAP-specific tracer molecules. PET- and corresponding MRI-scans were co-registrated. 3d volumetric segmentations were performed of T2w/FLAIR lesions and contrast enhancing lesions within co-registrated MRI slides. Signal intensity values of FAP-specific PET signaling, ADC and rCBV were analyzed for their pixel wise correlation in each patient. Pooled estimates of the correlation coefficients were calculated by using the Fisher z-transformation. RESULTS: FAP-specific PET signals showed a moderately positive correlation with rCBV values which is more pronounced within the T2w/FLAIR lesion (pooled correlation 0,229) than in the contrast enhancing tumor region (pooled correlation 0.09). FAP-specific PET signals showed no correlation with ADC values. CONCLUSIONS: The moderately positive correlation of FAP-specific signals with rCBV values in MRI indicates that FAP-signaling is not independent from perfusion, but also does not only reflect intratumoral perfusion differences. The missing correlation of FAP-specific signals with ADC indicates that FAP-specific imaging does not reflect cell density, but the spot-like expression of FAP in glioblastomas. The clinical value of FAP-specific imaging needs further investigation.

Vascular habitat analysis based on dynamic susceptibility contrast perfusion MRI predicts IDH mutation status and prognosis in high-grade gliomas.

OBJECTIVE: The current study aimed to evaluate the clinical practice for hemodynamic tissue signature (HTS) method in IDH genotype prediction in three groups derived from high-grade gliomas. METHODS: Preoperative MRI examinations of 44 patients with known grade and IDH genotype were assigned into three study groups: glioblastoma multiforme, grade III, and high-grade gliomas. Perfusion parameters were analyzed and were used to automatically draw the four reproducible habitats (high-angiogenic enhancing tumor habitats, low-angiogenic enhancing tumor habitats, infiltrated peripheral edema habitats, vasogenic peripheral edema habitats) related to vascular heterogeneity. These four habitats were then compared between inter-patient with IDH mutation and their wild-type counterparts at these three groups, respectively. The discriminating potential for HTS in assessing IDH mutation status prediction was assessed by ROC curves. RESULTS: Compared with IDH wild type, IDH mutation had significantly decreased relative cerebral blood volume (rCBV) at the high-angiogenic enhancing tumor habitats and low-angiogenic enhancing tumor habitats. ROC analysis revealed that the rCBVs in habitats had great ability to discriminate IDH mutation from their wild type in all groups. In addition, the Kaplan-Meier survival analysis yielded significant differences for the survival times observed from the populations dichotomized by low (< 4.31) and high (> 4.31) rCBV in the low-angiogenic enhancing tumor habitat. CONCLUSIONS: The HTS method has been proven to have high prediction capabilities for IDH mutation status in high-grade glioma patients, providing a set of quantifiable habitats associated with tumor vascular heterogeneity. KEY POINTS: • The HTS method has a high accuracy for molecular stratification prediction for all subsets of HGG. • The HTS method can give IDH mutation-related hemodynamic information of tumor-infiltrated and vasogenic edema. • IDH-relevant rCBV difference in habitats will be a great prognosis factor in HGG.

A novel visual ranking system based on arterial spin labeling perfusion imaging for evaluating perfusion disturbance in patients with ischemic stroke.

We developed a visual ranking system by combining the parenchymal perfusion deficits (PPD) and hyperintense vessel signals (HVS) on arterial spin labeling (ASL) imaging. This study aimed to assess the performance of this ranking system by correlating with subtypes classified based on dynamic susceptibility contrast (DSC) imaging for evaluating the perfusion disturbance observed in patients with ischemic stroke. 32 patients with acute or subacute infarcts detected by DSC imaging were reviewed. Each patient's brain was divided into 12 areas. ASL ranks were defined by the presence (+) or absence (-) of PPD/HVS as follows; I:-/-, II:-/+, III: +/+, and IV: +/-. DSC imaging findings were categorized based on cerebral blood flow (CBF) and time to peak (TTP) as normal (normal CBF/TTP), mismatched (normal CBF/delayed TTP), and matched (decreased CBF/delayed TTP). Two reviewers rated perfusion abnormalities in the total of 384 areas. The four ASL ranks correlated well with the DSC subtypes (Spearman's r = 0.82). The performance of ASL ranking system was excellent as indicated by the area under the curve value of 0.94 using either matched or mismatched DSC subtype as the gold standard and 0.97 using only the matched DSC subtype as the gold standard. The two methods were in good-to-excellent agreement (maximum κ-values, 0.86). Inter-observer agreement was excellent (κ-value, 0.98). Although the number of patients was small and the number of dropouts was high, our proposed, ASL-based visual ranking system represented by PPD and HVS provides good, graded estimates of perfusion disturbance that agree well with those obtained by DSC perfusion imaging.

Percentage signal intensity recovery: A step ahead of rCBV in DSC MR perfusion imaging for the differentiation of common neoplasms of brain.

CONTEXT: Relative cerebral blood volume (rCBV) and percentage signal recovery (PSR) obtained from T2* dynamic susceptibility contrast magnetic resonance imaging are important parameters for brain tumor assessment. AIM: To study the accuracy of PSR in the differentiation of low-grade glioma, high-grade glioma, lymphoma, and metastases particularly in comparison to rCBV. SETTINGS AND DESIGN: Retrospective observational study. SUBJECTS AND METHODS: Study included pathologically confirmed cases of 10 low-grade glioma, 22 high-grade glioma, 6 lymphoma, and 12 metastases (Total 50). PSR, relative PSR (rPSR), and rCBV were calculated. STATISTICAL ANALYSIS USED: Accuracy of these parameters studied statistically using analysis of variance and ROC (Receiver operating characteristic) curves. RESULTS: rCBV was higher in metastases (3.45 ± 2.82) and high-grade glioma (3.47 ± 1.62), whereas was low in lymphoma (1.03 ± 0.74) and low-grade glioma (1.43 ± 0.47) with P value of 0.030. PSR was low in metastases (48 ± 16.18), intermediate in glioma (73.24 ± 6.39 and 88.26 ± 6.05, high and low grade), and high in lymphoma (112.16 ± 10.57) with P value < 0.000. rPSR was higher for lymphoma (1.73 ± 0.57) than high-grade glioma (0.85 ± 0.11) and metastasis (0.69 ± 0.19) with P value <.000. Area under ROC for PSR was greater than rCBV in differentiating metastases from lymphoma (1.00 vs 0.13), high-grade glioma from lymphoma (1.00 vs 0.38), high-grade glioma from metastases (0.89 vs 0.58), and high-grade glioma from low-grade glioma (0.96 vs 0.03) with excellent curve characteristics. F values for PSR and rPSR from ANOVA analysis were 71.47 and 36.77, was better than rCBV (3.84) in differentiating these groups. CONCLUSIONS: Percentage of signal recovery shows low recovery values in metastases, intermediate recovery values in glioma, and overshoot in lymphoma. PSR values show lower overlap than rCBV between lymphoma and metastases; and between high grade glioma and metastases. PSR difference is also higher than rCBV between low- and high-grade gliomas. Hence, PSR can potentially help as an additional perfusion parameter in the preoperative differentiation of these tumors.