Susceptibility Contrast Magnetic Resonance Imaging Research Articles

Cerebral hemodynamics as biomarkers for neuropathic pain in rats: a longitudinal study using a spinal nerve ligation model.

Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. Furthermore, by identifying multiple regional hemodynamic features that are the most distinct between SNL and sham groups, where the sham group underwent only an incision without SNL, it may be possible to classify the SNL group regardless of when the onset of pain occurs. We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.

Influence of arterial transit time delays on the differentiation between tumor progression and pseudoprogression in glioblastoma by arterial spin labeling magnetic resonance imaging.

Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) have shown potential for differentiating tumor progression from pseudoprogression. For pseudocontinuous ASL with a single postlabeling delay, the presence of delayed arterial transit times (ATTs) could affect the evaluation of ASL-MRI perfusion data. In this study, the influence of ATT artifacts on the perfusion assessment and differentiation between tumor progression and pseudoprogression were studied. This study comprised 66 adult patients (mean age 60 ± 13 years; 40 males) with a histologically confirmed glioblastoma who received postoperative radio (chemo)therapy. ASL-MRI and DSC-MRI scans were acquired at 3months postradiotherapy as part of the standard clinical routine. These scans were visually scored regarding (i) the severity of ATT artifacts (%) on the ASL-MRI scans only, scored by two neuroradiologists; (ii) perfusion of the enhancing tumor lesion; and (iii) radiological evaluation of tumor progression versus pseudoprogression by one neuroradiologist. The final outcome was based on combined clinical and radiological follow-up until 9months postradiotherapy. ATT artifacts were identified in all patients based on the mean scores of two raters. A significant difference between the radiological evaluation of ASL-MRI and DSC-MRI was observed only for ASL images with moderate ATT severity (30%-65%). The perfusion assessment showed ASL-MRI tending more towards hyperperfusion than DSC-MRI in the case of moderate ATT artifacts. In addition, there was a significant difference between the prediction of tumor progression with ASL-MRI and the final outcome in the case of severe ATT artifacts (McNemar test, p= 0.041). Despite using ASL imaging parameters close to the recommended settings, ATT artifacts frequently occur in patients with treated brain tumors. Those artifacts could hinder the radiological evaluation of ASL-MRI data and the detection of true disease progression, potentially affecting treatment decisions for patients with glioblastoma.

Macro- and microvascular contributions to cerebral structural alterations in patients with asymptomatic carotid artery stenosis.

Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging. SVD-related alterations were assessed using free water (FW), FW-corrected DTI, and peak-width of skeletonized mean diffusivity (PSMD). Furthermore, cortical thickness, cerebral blood flow (CBF), and capillary transit time heterogeneity (CTH) were analyzed. Ipsilateral to the stenosis, cortical thickness was significantly decreased in the posterior dorsal cingulate cortex (p = 0.024) and temporal pole (p = 0.028). ICAS patients exhibited elevated PSMD (p = 0.005), FW (p < 0.001), and contralateral alterations in FW-corrected DTI metrics. We found significantly lateralized CBF (p = 0.011) and a tendency for lateralized CTH (p = 0.067) in the white matter (WM) related to ICAS. Elevated PSMD and FW may indicate a link between SVD and WM changes. Contralateral alterations were seen in FW-corrected DTI, whereas hemodynamic and cortical changes were mainly ipsilateral, suggesting SVD might influence global brain changes concurrent with ICAS-related hemodynamic alterations.

Creation of a Simulated Sequence of Dynamic Susceptibility Contrast—Magnetic Resonance Imaging Brain Scans as a Tool to Verify the Quality of Methods for Diagnosing Diseases Affecting Brain Tissue Perfusion

DSC-MRI examination is one of the best methods of diagnosis for brain diseases. For this purpose, the so-called perfusion parameters are defined, of which the most used are CBF, CBV, and MTT. There are many approaches to determining these parameters, but regardless of the approach, there is a problem with the quality assessment of methods. To solve this problem, this article proposes virtual DSC-MRI brain examination, which consists of two steps. The first step is to create curves that are typical for DSC-MRI studies and characteristic of different brain regions, i.e., the gray and white matter, and blood vessels. Using perfusion descriptors, the curves are classified into three sets, which give us the model curves for each of the three regions. The curves corresponding to the perfusion of different regions of the brain in a suitable arrangement (consistent with human anatomy) form a model of the DSC-MRI examination. In the created model, one knows in advance the values of the complex perfusion parameters, as well as basic perfusion descriptors. The shown model study can be disturbed in a controlled manner—not only by adding noise, but also by determining the location of disturbances that are characteristic of specific brain diseases.

Assessment of the Effects of Sodium Nitroprusside Administered Via Intracranial Subdural Catheters on the Cerebral Blood Flow and Lactate Using Dynamic Susceptibility Contrast Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy in a Pig Cardiac Arrest Model.

Background Cerebral blood flow (CBF) is impaired in the early phase after return of spontaneous circulation. Sodium nitroprusside (SNP) administration via intracranial subdural catheters improves cerebral cortical microcirculation. We determined whether the SNP treatment improves CBF in the subcortical tissue and evaluated the effects of this treatment on cerebral lactate. Methods and Results Sixty minutes after return of spontaneous circulation following 14 minutes of untreated cardiac arrest, 14 minipigs randomly received 4 mg SNP or saline via intracranial subdural catheters. CBF was measured in regions of interest within the cerebrum and thalamus using dynamic susceptibility contrast-magnetic resonance imaging. After return of spontaneous circulation, CBF was expressed as a percentage of the baseline value. In the saline group, the %CBF in the regions of interest within the cerebrum remained at approximately 50% until 3.5 hours after return of spontaneous circulation, whereas %CBF in the thalamic regions of interest recovered to approximately 73% at this time point. The percentages of the baseline values in the cortical gray matter and subcortical white matter were higher in the SNP group (group effect P=0.026 and 0.025, respectively) but not in the thalamus. The cerebral lactate/creatine ratio measured using magnetic resonance spectroscopy increased over time in the saline group but not in the SNP group (group-time interaction P=0.035). The thalamic lactate/creatine ratio was similar in the 2 groups. Conclusions SNP administered via intracranial subdural catheters improved CBF not only in the cortical gray matter but also in the subcortical white matter. The CBF improvement by SNP was accompanied by a decrease in cerebral lactate.

Capillary dysfunction in healthy elderly APOE ε4 carriers with raised brain Aβ deposition.

Capillary dysfunction, characterized by disturbances in capillary blood flow distribution, might be an overlooked factor in the development of Alzheimer's disease (AD). This study investigated microvascular blood flow in preclinical and prodromal AD individuals. Using dynamic susceptibility contrast magnetic resonance imaging and positron emission tomography, we examined alterations in microvascular circulation and levels of Aβ deposition in two independent cohorts of APOE ε4 carriers. Capillary dysfunction was elevated in both prodromal and preclinical AD individuals compared to age-matched controls. Additionally, the prodromal group exhibited higher levels of capillary dysfunction compared to the preclinical group. These findings suggest that capillary dysfunction can be detected at the preclinical stage of AD and indicates a worsening of capillary dysfunction throughout the AD continuum. Understanding the interaction between capillary dysfunction and Aβ could provide insights into the relationship between cardiovascular risk factors and the development of AD. Alzheimer's disease (AD) is associated with disturbances in microvascular circulation. Capillary dysfunction can be detected in preclinical AD. As cognitive symptoms progress in prodromal AD, capillary dysfunction worsens. Capillary dysfunction may impede the clearance of beta-amyloid (Aβ). Capillary dysfunction might contribute to the development of AD.

Dynamic susceptibility contrast perfusion-weighted and diffusion-weighted magnetic resonance imaging findings in pilocytic astrocytoma and H3.3 and H3.1 variant diffuse midline glioma, H3K27-altered.

This study compared the dynamic susceptibility contrast (DSC) magnetic resonance imaging parameters and apparent diffusion coefficient (ADC) between pilocytic astrocytoma (PA) and diffuse midline glioma, H3K27-altered (DMG) variants. The normalized relative cerebral blood volume (nrCBV), normalized relative flow (nrCBF), percentile signal recovery (PSR), and normalized mean ADC (nADCmean) of 23 patients with midline PAs (median age, 13 years [range, 1-71 years]; 13 female patients) and 40 patients with DMG (8.5 years [1-35 years]; 19 female patients), including 35 patients with H3.3- and five patients with H3.1-mutant tumors, treated between January 2016 and May 2022 were statistically compared. DMG had a significantly lower nADCmean (median: 1.48 vs. 1.96; p = 0.00075) and lower PSR (0.97 vs. 1.23, p = 0.13) but higher nrCBV and nrCBF (1.66 vs. 1.17, p = 0.058, respectively, and 1.87 vs. 1.19, p = 0.028, respectively) than PA. The H3.3 variant had a lower nADCmean than the H3.1 variant (1.46 vs. 1.80, p = 0.10). DMG had lower ADC and PSR and higher rCBV and rCBF than PA. The H3.3 variant had a lower ADC than the H3.1 variant. Recognizing the differences and similarities in the DSC parameters and ADC between these tumors may help presurgical diagnosis.

Surgical outcomes following encephaloduroarteriosynangiosis in moyamoya disease associated with hyperhomocysteinemia.

This study investigated the effect of indirect revascularization surgery in adult patients with moyamoya disease (MMD) complicated with hyperhomocysteinemia (HHcy), and the effect of HHcy on the progression of adult MMD. A retrospective case-control study was conducted in patients with MMD, with or without HHcy (n=123). Postoperative collateral angiogenesis was evaluated using the Matsushima grading system and disease progression using the Suzuki staging system. Cerebral blood flow was evaluated before and after surgery using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and neurological function prognosis using the improved Rankin score (mRS). Univariate and multivariate logistic regression analyses were performed to determine risk factors for the clinical outcomes. There was no significant difference in the Suzuki stage composition ratios between the HHcy group and the non-HHcy group before and after surgery. Non-HHcy patients were more likely to grow new collateral circulating vessels after encephaloduroarteriosynangiosis (EDAS). Moreover, postoperative DSC-MRI indicated that the time to peak significantly improved. HHcy level may be a specific predictor of adverse clinical outcomes after EDAS in patients with MMD and a risk factor for poor collateral circulation and poor prognosis. Patients with MMD complicated with HHcy need to strictly control homocysteine levels before EDAS surgery.

Predictors of Stroke Outcomes in Conservatively Treated Patients With Moyamoya Disease: A Follow-up MRI Study.

Little is known about the association between stroke and imaging and clinical features in conservatively treated patients with moyamoya disease (MMD). To investigate independent risk factors for stroke in conservatively treated patients with MMD during a long-term follow-up. Prospective study. One hundred sixty conservatively managed patients with MMD (median age 46 years, 89 male). Time of flight, turbo inversion recovery magnitude T1WI, turbo spin echo (TSE) T2WI, echo-planar imaging DWI, T2-fluid attenuated inversion recovery, dynamic susceptibility contrast-magnetic resonance imaging, and pre- and post-contrast 3D TSE T1WI sequences at 3.0 Tesla. Patients were assessed at baseline and followed yearly. Ischemic and hemorrhagic stroke incidence rates were determined. Multiple demographic, clinical (modified Rankin score [mRS]), and cerebral imaging (cerebral blood volume [CBV] and concentric enhancement of arterial wall) factors at baseline were considered as potential predictors of stroke during the follow-up period. Univariable and multivariable Cox proportional hazards models to calculate the hazard ratios (HRs) and corresponding 95% confidence interval (CI) for stroke. Cumulative risk of stroke was estimated by the Kaplan-Meier product-limit method. A P value <0.05 was considered statistically significant. The median follow-up duration was 47 months. During the follow-up period, 18 (11.25%) patients experienced stroke events (13 [8.13%] ischemic, 5 [3.12%] hemorrhagic). Univariable analysis showed that 11 factors were significantly associated with stroke. After adjustment for clinical characteristics, multivariable analysis showed that mRS score ≥3 (HR, 1.99; 95% CI, 1.26-3.14), decreased CBV (HR, 5.31; 95% CI, 2.32-12.13), and concentric enhancement of the arterial wall (HR, 4.16; 95% CI, 1.55-11.15) were significantly associated with stroke. Decreased CBV, mRS score ≥ 3, and concentric enhancement of the arterial wall were significantly associated with increased incidence of stroke in conservatively treated MMD. 2 TECHNICAL EFFICACY: Stage 4.

Using carpet plots to analyze blood transit times in the brain during hypercapnic challenge magnetic resonance imaging.

Blood arrival time and blood transit time are useful metrics in characterizing hemodynamic behaviors in the brain. Functional magnetic resonance imaging in combination with a hypercapnic challenge has been proposed as a non-invasive imaging tool to determine blood arrival time and replace dynamic susceptibility contrast (DSC) magnetic resonance imaging, a current gold-standard imaging tool with the downsides of invasiveness and limited repeatability. Using a hypercapnic challenge, blood arrival times can be computed by cross-correlating the administered CO2 signal with the fMRI signal, which increases during elevated CO2 due to vasodilation. However, whole-brain transit times derived from this method can be significantly longer than the known cerebral transit time for healthy subjects (nearing 20s vs. the expected 5-6s). To address this unrealistic measurement, we here propose a novel carpet plot-based method to compute improved blood transit times derived from hypercapnic blood oxygen level dependent fMRI, demonstrating that the method reduces estimated blood transit times to an average of 5.32s. We also investigate the use of hypercapnic fMRI with cross-correlation to compute the venous blood arrival times in healthy subjects and compare the computed delay maps with DSC-MRI time to peak maps using the structural similarity index measure (SSIM). The strongest delay differences between the two methods, indicated by low structural similarity index measure, were found in areas of deep white matter and the periventricular region. SSIM measures throughout the remainder of the brain reflected a similar arrival sequence derived from the two methods despite the exaggerated spread of voxel delays computed using CO2 fMRI.

Image-to-image generative adversarial networks for synthesizing perfusion parameter maps from DSC-MR images in cerebrovascular disease.

Stroke is a major cause of death or disability. As imaging-based patient stratification improves acute stroke therapy, dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) is of major interest in image brain perfusion. However, expert-level perfusion maps require a manual or semi-manual post-processing by a medical expert making the procedure time-consuming and less-standardized. Modern machine learning methods such as generative adversarial networks (GANs) have the potential to automate the perfusion map generation on an expert level without manual validation. We propose a modified pix2pix GAN with a temporal component (temp-pix2pix-GAN) that generates perfusion maps in an end-to-end fashion. We train our model on perfusion maps infused with expert knowledge to encode it into the GANs. The performance was trained and evaluated using the structural similarity index measure (SSIM) on two datasets including patients with acute stroke and the steno-occlusive disease. Our temp-pix2pix architecture showed high performance on the acute stroke dataset for all perfusion maps (mean SSIM 0.92-0.99) and good performance on data including patients with the steno-occlusive disease (mean SSIM 0.84-0.99). While clinical validation is still necessary for future studies, our results mark an important step toward automated expert-level perfusion maps and thus fast patient stratification.

Comparative study between dynamic susceptibility contrast magnetic resonance imaging and arterial spin labelling perfusion in differentiating low-grade from high-grade brain tumours.

Our aim was to distinguish between low-grade and high-grade brain tumours on the basis of dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion and arterial spin labelling (ASL) perfusion and to compare DSC and ASL techniques. Forty-one patients with brain tumours were evaluated by 3-Tesla MRI. Conventional and perfusion MRI imaging with a 3D pseudo-continuous ASL (PCASL) and DSC perfusion maps were evaluated. Three ROIs were placed to obtain cerebral blood value (CBV) and cerebral blood flow (CBF) in areas of maximum perfusion in brain tumour and normal grey matter. Histopathological diagnosis was considered as the reference. ROC analysis was performed to compare the diagnostic performance and to obtain a feasible cut-off value of perfusion parameters to differentiate low-grade and high-grade brain tumours. Normalised perfusion parameters with grey matter (rCBF or rCBV lesion/NGM) of malignant lesions were significantly higher than those of benign lesions in both DSC (normalised rCBF of 2.16 and normalised rCBV of 2.63) and ASL (normalised rCBF of 2.22) perfusion imaging. The normalised cut-off values of DSC (rCBF of 1.1 and rCBV of 1.4) and ASL (rCBF of 1.3) showed similar specificity and near similar sensitivity in distinguishing low-grade and high-grade brain tumours. Quantitative analysis of perfusion parameters obtained by both DSC and ASL perfusion techniques can be reliably used to distinguish low-grade and high-grade brain tumours. Normalisation of these values by grey matter gives us more reliable parameters, eliminating the different technical parameters involved in both the techniques.

Abnormal cerebral hemodynamics and blood-brain barrier permeability detected with perfusion MRI in systemic lupus erythematosus patients

ObjectiveDynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) has previously shown alterations in cerebral perfusion in patients with systemic lupus erythematosus (SLE). However, the results have been inconsistent, in particular regarding neuropsychiatric (NP) SLE. Thus, we investigated perfusion-based measures in different brain regions in SLE patients with and without NP involvement, and additionally, in white matter hyperintensities (WMHs), the most common MRI pathology in SLE patients. Materials and methodsWe included 3 T MRI images (conventional and DSC) from 64 female SLE patients and 19 healthy controls (HC). Three different NPSLE attribution models were used: the Systemic Lupus International Collaborating Clinics (SLICC) A model (13 patients), the SLICC B model (19 patients), and the American College of Rheumatology (ACR) case definitions for NPSLE (38 patients). Normalized cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were calculated in 26 manually drawn regions of interest and compared between SLE patients and HC, and between NPSLE and non-NPSLE patients. Additionally, normalized CBF, CBV and MTT, as well as absolute values of the blood-brain barrier leakage parameter (K2) were investigated in WMHs compared to normal appearing white matter (NAWM) in the SLE patients. ResultsAfter correction for multiple comparisons, the most prevalent finding was a bilateral significant decrease in MTT in SLE patients compared to HC in the hypothalamus, putamen, right posterior thalamus and right anterior insula. Significant decreases in SLE compared to HC were also found for CBF in the pons, and for CBV in the bilateral putamen and posterior thalamus. Significant increases were found for CBF in the posterior corpus callosum and for CBV in the anterior corpus callosum. Similar patterns were found for both NPSLE and non-NPSLE patients for all attributional models compared to HC. However, no significant perfusion differences were revealed between NPSLE and non-NPSLE patients regardless of attribution model. The WMHs in SLE patients showed a significant increase in all perfusion-based metrics (CBF, CBV, MTT and K2) compared to NAWM. ConclusionOur study revealed perfusion differences in several brain regions in SLE patients compared to HC, independently of NP involvement. Furthermore, increased K2 in WMHs compared to NAWM may indicate blood-brain barrier dysfunction in SLE patients. We conclude that our results show a robust cerebral perfusion, independent from the different NP attribution models, and provide insight into potential BBB dysfunction and altered vascular properties of WMHs in female SLE patients. Despite SLE being most prevalent in females, a generalization of our conclusions should be avoided, and future studies including all sexes are needed.

Test-retest analysis of cerebral oxygen extraction estimates in healthy volunteers: comparison of methods based on quantitative susceptibility mapping and dynamic susceptibility contrast magnetic resonance imaging

BackgroundEstimation of the oxygen extraction fraction (OEF) by quantitative susceptibility mapping (QSM) magnetic resonance imaging (MRI) is promising but requires systematic evaluation. Extraction of OEF-related information from the tissue residue function in dynamic susceptibility contrast MRI (DSC-MRI) has also been proposed. In this study, whole-brain OEF repeatability was investigated, as well as the relationships between QSM-based OEF and DSC-MRI-based parameters, i.e., mean transit time (MTT) and an oxygen extraction index, referred to as apparent OEF (AOEF). MethodTest-retest data were obtained from 20 healthy volunteers at 3 T. QSM maps were reconstructed from 3D gradient-echo MRI phase data, using morphology-enabled dipole inversion. DSC-MRI was accomplished using gradient-echo MRI at a temporal resolution of 1.24 s. ResultsThe whole-brain QSM-based OEF was (40.4±4.8) % and, in combination with a previously published cerebral blood flow (CBF) estimate, this corresponds to a cerebral metabolic rate of oxygen level of CMRO2 = 3.36 ml O2/min/100 g. The intra-class correlation coefficient [ICC(2,1)] for OEF test-retest data was 0.73. The MTT-versus-OEF and AOEF-versus-OEF relationships showed correlation coefficients of 0.61 (p = 0.004) and 0.52 (p = 0.019), respectively. DiscussionQSM-based OEF showed a convincing absolute level and good test-retest results in terms of the ICC. Moderate to good correlations between QSM-based OEF and DSC-MRI-based parameters were observed. The present results constitute an indicator of the level of robustness that can be achieved without applying extraordinary resources in terms of MRI equipment, imaging protocol, QSM reconstruction, and OEF analysis.

339 Relationships of Jugular Bulb Parameters Used as Indicators of Cerebral Perfusion and Metabolism With Cerebral Perfusion and Metabolism After Resuscitation from Cardiac Arrest: A Post-hoc Analysis of Experimental Studies Using a Minipig Model

339 Relationships of Jugular Bulb Parameters Used as Indicators of Cerebral Perfusion and Metabolism With Cerebral Perfusion and Metabolism After Resuscitation from Cardiac Arrest: A Post-hoc Analysis of Experimental Studies Using a Minipig Model

Arterial input functions in dynamic susceptibility contrast MRI (DSC-MRI) in longitudinal evaluation of brain metastases.

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) could be helpful to separate true disease progression from pseudo-progression in brain metastases when assessing the need for retreatment. However, the selection of arterial input functions (AIFs) is not standardized for analysis, limiting its use for this application. To compare population-based AIFs, AIFs specific to each patient, and AIFs specific to every visit in the longitudinal follow-up of brain metastases. Longitudinal data were collected from eight patients before treatment (6 of 8 patients) and after treatment (6-17 visits). Imaging was performed using a 1.5-T MRI system. Lesions were segmented by subtracting precontrast images from postcontrast images. Cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were computed, and Pearson's product moment correlation coefficients were calculated to evaluate similarity of DSC parameters dependent on various AIF choices across time. AIF shape characteristics were compared. Parameter differences between white matter (WM) and gray matter (GM) were obtained to determine which AIF choice maximizes tissue differentiation. Although DSC parameters follow similar patterns in time, the various AIF selections cause large parameter variations with relative standard deviations of up to ±60%. AIFs sampled in one patient across sessions more similar in shape than AIFs sampled across patients. Estimates of rCBV based on scan-specific AIFs differentiated better between perfusion in WM and GM than patient-specific or population-based AIFs (P ≤ 0.02). Results indicate that scan-specific AIFs are the best choice for DSC-MRI parameter estimations in the longitudinal follow-up of brain metastases.

Hemodynamic Imaging in Cerebral Diffuse Glioma-Part A: Concept, Differential Diagnosis and Tumor Grading.

Simple SummaryDiffuse gliomas, and glioblastomas, in particular, represent a diagnostic and clinical challenge. Standard neuroimaging continues to have many limitations for accurate diagnostic assessment, resection planning and treatment follow-up. The present two-review series comprehensively summarizes recent evidence on hemodynamic imaging applications in the context of diffuse cerebral glioma. Part A provides an overview of the concepts underlying hemodynamic imaging modalities and critically discusses the diffuse glioma differential diagnosis and tumor grading results reported in the literature.Diffuse gliomas are the most common primary malignant intracranial neoplasms. Aside from the challenges pertaining to their treatment—glioblastomas, in particular, have a dismal prognosis and are currently incurable—their pre-operative assessment using standard neuroimaging has several drawbacks, including broad differentials diagnosis, imprecise characterization of tumor subtype and definition of its infiltration in the surrounding brain parenchyma for accurate resection planning. As the pathophysiological alterations of tumor tissue are tightly linked to an aberrant vascularization, advanced hemodynamic imaging, in addition to other innovative approaches, has attracted considerable interest as a means to improve diffuse glioma characterization. In the present part A of our two-review series, the fundamental concepts, techniques and parameters of hemodynamic imaging are discussed in conjunction with their potential role in the differential diagnosis and grading of diffuse gliomas. In particular, recent evidence on dynamic susceptibility contrast, dynamic contrast-enhanced and arterial spin labeling magnetic resonance imaging are reviewed together with perfusion-computed tomography. While these techniques have provided encouraging results in terms of their sensitivity and specificity, the limitations deriving from a lack of standardized acquisition and processing have prevented their widespread clinical adoption, with current efforts aimed at overcoming the existing barriers.

Penumbra Detection With Oxygen Extraction Fraction Using Magnetic Susceptibility in Patients With Acute Ischemic Stroke.

BackgroundThe oxygen extraction fraction (OEF) has been applied to identify ischemic penumbral tissue, but is difficult to use in an urgent care setting. This study aimed to investigate whether an OEF map generated via magnetic resonance quantitative susceptibility mapping (QSM) could help identify the ischemic penumbra in patients with acute ischemic stroke.Materials and MethodsThis prospective imaging study included 21 patients with large anterior circulation vessel occlusion who were admitted <24 h after stroke onset and 21 age-matched healthy controls. We identified the ischemic penumbra as the region with a Tmax of >6 s during dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) and calculated the perfusion-core mismatch ratio between the ischemic penumbra and infarct core volumes. The OEF values were measured based on magnetic susceptibility differences between the venous structures and brain tissues using rapid QSM acquisition. Volumes with increased OEF values were compared to the ischemic penumbra volumes using an anatomical template.ResultsEleven patients had a perfusion-core mismatch ratio of ≥1.8, and reperfusion therapy was recommended. In these patients, the volumes with increased OEF values of >51.5%, which was defined using the anterior circulation territory OEF values from the 21 healthy controls, were positively correlated with the ischemic penumbra volumes (r = 0.636, 95% CI: 0.059 to 0.895, P = 0.035) and inversely correlated with the 30-day change in the National Institutes of Health Stroke Scale scores (r = −0.624, 95% CI: −0.891 to −0.039, P = 0.041).ConclusionTissue volumes with increased OEF values could predict ischemic penumbra volumes based on DSC-MRI, highlighting the potential of the QSM-derived OEF map as a penumbra biomarker to guide treatment selection in patients with acute ischemic stroke.

Non-parametric deconvolution using Bézier curves for quantification of cerebral perfusion in dynamic susceptibility contrast MRI

ObjectiveDeconvolution is an ill-posed inverse problem that tends to yield non-physiological residue functions R(t) in dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). In this study, the use of Bézier curves is proposed for obtaining physiologically reasonable residue functions in perfusion MRI.Materials and methodsCubic Bézier curves were employed, ensuring R(0) = 1, bounded-input, bounded-output stability and a non-negative monotonically decreasing solution, resulting in 5 parameters to be optimized. Bézier deconvolution (BzD), implemented in a Bayesian framework, was tested by simulation under realistic conditions, including effects of arterial delay and dispersion. BzD was also applied to DSC-MRI data from a healthy volunteer.ResultsBézier deconvolution showed robustness to different underlying residue function shapes. Accurate perfusion estimates were observed, except for boxcar residue functions at low signal-to-noise ratio. BzD involving corrections for delay, dispersion, and delay with dispersion generally returned accurate results, except for some degree of cerebral blood flow (CBF) overestimation at low levels of each effect. Maps of mean transit time and delay were markedly different between BzD and block-circulant singular value decomposition (oSVD) deconvolution.DiscussionA novel DSC-MRI deconvolution method based on Bézier curves was implemented and evaluated. BzD produced physiologically plausible impulse response, without spurious oscillations, with generally less CBF underestimation than oSVD.

Heterogeneity of tau deposition and microvascular involvement in MCI and AD.

Recent preclinical and clinical studies have highlighted the role of tau pathology in the impaired cerebrovascular function frequently observed in mild cognitive impairment (MCI) and Alzheimer's disease (AD). These studies typically report on cerebrovascular abnormalities, disease severity, and/or tau deposition in only a few brain regions susceptible to AD pathology. Animal models of tauopathy demonstrate extended tau-driven alterations in capillary physiology, including aberrant angiogenesis, suggesting the interaction between tau and perfusion may be more complex and heterogeneous than others have presented. This study is the first to date to inspect the extent of heterogeneity in microvascular perfusion associated with tau deposition in MCI and AD patients. Seven subjects with cognitive impairment received Flortaucipir positron emission tomography (PET) imaging to measure tau neurofibrillary tangle deposition. Microvascular perfusion was quantified using spin-echo dynamic susceptibility contrast (SE-DSC) magnetic resonance imaging (MRI), which is particularly sensitive to signal from capillaries (radius <10µm). To evaluate macrovascular perfusion for comparison, gradient echo DSC (GE-DSC) and pseudocontinuous arterial spin labeling (PCASL) magnetic resonance imaging (MRI) were also acquired. Cerebral blood flow (CBF) maps were derived from SE-DSC, GE-DSC, and PCASL imaging. Capillary transit heterogeneity (CTH) and oxygen extraction fraction (OEF) maps were derived from SE-DSC and GE-DSC MRI. Functional maps were visually inspected in volumetric slices and cortical surface projections, with summary statistics calculated across cortical surface vertices per subject. Across the seven subjects with MCI or AD (6 MCI/1 AD, 4M/3F, ages 66-85), high tau-PET standardized uptake value ratio (SUVR) signal was primarily observed in the inferior and middle temporal and parietal cortices, with marked uptake in the occipital cortex in one subject. Tau accumulation was spatially associated with highly variable patterns of CBF and OEF throughout the cortex, with marked CTH hotspots in the periventricular white matter of several subjects. Cortical thickness patterns were consistent across subjects despite the microvascular perfusion heterogeneity, indicating that such vascular changes are unlikely to be driven by atrophy alone. Preliminary multi-modal imaging data suggest complex associations between tau pathology and microvascular perfusion abnormalities beyond regions susceptible to AD.