Feasibility and safety of intraoperative BOLD functional MRI cerebrovascular reactivity to evaluate extracranial-to-intracranial bypass efficacy.

Blood oxygenation level-dependent functional MRI cerebrovascular reactivity (BOLD-CVR) is a contemporary technique to assess brain tissue hemodynamic changes after extracranial- intracranial (EC-IC) bypass flow augmentation surgery. The authors conducted a preliminary study to investigate the feasibility and safety of intraoperative 3-T MRI BOLD-CVR after EC-IC bypass flow augmentation surgery. Five consecutive patients selected for EC-IC bypass revascularization underwent an intraoperative BOLD-CVR examination to assess early hemodynamic changes after revascularization and to confirm the safety of this technique. All patients had a normal postoperative course, and none of the patients exhibited complications or radiological alterations related to prolonged anesthesia time. In addition to intraoperative flow measurements of the bypass graft, BOLD-CVR maps added information on the hemodynamic status and changes at the brain tissue level. Intraoperative BOLD-CVR is feasible and safe in patients undergoing EC-IC bypass revascularization. This technique can offer immediate hemodynamic feedback on brain tissue revascularization after bypass flow augmentation surgery.

Staging Hemodynamic Failure With Blood Oxygen-Level-Dependent Functional Magnetic Resonance Imaging Cerebrovascular Reactivity: A Comparison Versus Gold Standard (15O-)H2O-Positron Emission Tomography.

BACKGROUND AND PURPOSE: Increased stroke risk correlates with hemodynamic failure, which can be assessed with (15O-)H2O positron emission tomography (PET) cerebral blood flow (CBF) measurements. This gold standard technique, however, is not established for routine clinical imaging. Standardized blood oxygen-level-dependent (BOLD) functional magnetic resonance imaging+CO2 is a noninvasive and potentially widely applicable tool to assess whole-brain quantitative cerebrovascular reactivity (CVR). We examined the agreement between the 2 imaging modalities and hypothesized that quantitative CVR can be a surrogate imaging marker to assess hemodynamic failure. METHODS: Nineteen data sets of subjects with chronic cerebrovascular steno-occlusive disease (age, 60±11 years; 4 women) and unilaterally impaired perfusion reserve on Diamox-challenged (15O-)H2O PET were studied and compared with a standardized BOLD functional magnetic resonance imaging+CO2 examination within 6 weeks (8±19 days). Agreement between quantitative CBF- and CVR-based perfusion reserve was assessed. Hemodynamic failure was staged according to PET findings: stage 0: normal CBF, normal perfusion reserve; stage I: normal CBF, decreased perfusion reserve; and stage II: decreased CBF, decreased perfusion reserve. The BOLD CVR data set of the same subjects was then matched to the corresponding stage of hemodynamic failure. RESULTS: PET-based stage I versus stage II could also be clearly separated with BOLD CVR measurements (CVR for stage I 0.11 versus CVR for stage II -0.03; P<0.01). Hemispheric and middle cerebral artery territory difference analyses (ie, affected versus unaffected side) showed a significant correlation for CVR impairment in the affected hemisphere and middle cerebral artery territory (P<0.01, R2=0.47 and P=0.02, R2= 0.25, respectively). CONCLUSIONS: BOLD CVR corresponded well to CBF perfusion reserve measurements obtained with (15O-)H2O-PET, especially for detecting hemodynamic failure in the affected hemisphere and middle cerebral artery territory and for identifying hemodynamic failure stage II. BOLD CVR may, therefore, be considered for prospective studies assessing stroke risk in patients with chronic cerebrovascular steno-occlusive disease, in particular because it can potentially be implemented in routine clinical imaging.

Post-operative cardiovascular complications and time to recurrence in meningioma patients treated with versus without pre-operative embolization: a retrospective cohort study of 741 patients.

PURPOSE: Preoperative embolization of radiographically suspected meningiomas is often performed to facilitate tumor resection. Its effects on the subsequent disease course of meningioma patients have not been studied in detail and randomized trials are lacking. The purpose of this study was to explore associations of preoperative meningioma embolization with postoperative outcome. PATIENTS AND METHODS: Patients undergoing resection of an intracranial meningioma at the University Hospital Zurich 2000-2013 (N = 741) were reviewed for the inclusion of pre-operative embolization in the management strategy. Annotations included demographics, radiographic, surgical, histological and hematological parameters, cardiovascular risk factors, pre- and postoperative neurological function and gene methylation-based classification. Binary regression and Cox proportional hazards models were applied to determine factors associated with outcome. RESULTS: Pre-operative embolization was performed in 337 patients (42%). Cardiovascular events after surgery comprised mostly deep vein thrombosis (N = 39) and pulmonary embolisms (N = 64). On multivariate analyses of post-operative cardiovascular adverse events controlling for established risk factors, there were associations with embolization (OR 2.38, 95% CI 1.37-4.00), and with female gender (OR 2.18, 95% CI 1.17-4.08). Recurrence-free survival (RFS) of embolized patients was less favorable among patients with WHO grade II or grade III meningiomas (median RFS: 4.3 vs. 7.0 years, P = 0.029) or in patients with intermediate or malignant gene methylation subtype meningiomas (median RFS: 2.0 vs. 8.2 years, P = 0.005). CONCLUSION: Pre-operative meningioma embolization may cause adverse outcomes. Randomized trials to determine benefit-risk ratios are warranted to clarify the role of pre-operative embolization for the treatment of meningioma patients.

Cardiac-gated intravoxel incoherent motion diffusion-weighted magnetic resonance imaging for the investigation of intracranial cerebrospinal fluid dynamics in the lateral ventricle: a feasibility study.

PURPOSE: Intravoxel incoherent motion (IVIM) in diffusion-weighted magnetic resonance imaging (DW-MRI) attributes the signal attenuation to the molecular diffusion and to a faster pseudo-diffusion. Purpose of the study was to demonstrate the feasibility of IVIM for the investigation of intracranial cerebrospinal fluid (CSF) dynamics. METHODS: Cardiac-gated DW-MRI images with fifteen b-values (0-1300s/mm2) along three orthogonal directions (mediolateral (ML), anteroposterior (AP), and craniocaudal (CC)) were acquired during maximum systole and diastole in 10 healthy volunteers (6 males, mean age 36 ± 15 years). A pixel-wise bi-exponential fitting with an iterative nonparametric algorithm was carried out to calculate the following parameters: diffusion coefficient (D), fast diffusion coefficient (D*), and fraction of fast diffusion (f). Region of interest measurements were performed in both lateral ventricles. Comparison of IVIM parameters was performed among two cardiac cycle acquisitions and among the diffusion-encoding directions using a paired Student's t test. RESULTS: f significantly (p < 0.05) depended on the diffusion-encoding direction and on the cardiac cycle (diastole AP 0.30 ± 0.13, ML 0.22 ± 0.12, CC 0.26 ± 0.17; systole AP 0.45 ± 0.17, ML 0.34 ± 0.15, CC 0.40 ± 0.21). Neither a cardiac cycle nor a direction dependency was found among mean D values (which is in line with the expected intraventricular isotropic diffusion) and D* values (p > 0.05 each). CONCLUSION: The fraction of fast diffusion from IVIM is feasible to detect a direction-dependent and cardiac-dependent pulsatile CSF flow within the lateral ventricles allowing for quantitative monitoring of CSF dynamics. This technique might provide opportunities to further investigate the pathophysiology of various neurological disorders involving altered CSF dynamics.

Combining monoenergetic extrapolations from dual-energy CT with iterative reconstructions: reduction of coil and clip artifacts from intracranial aneurysm therapy.

PURPOSE: To compare and to combine iterative metal artifact reduction (MAR) and virtual monoenergetic extrapolations (VMEs) from dual-energy computed tomography (DECT) for reducing metal artifacts from intracranial clips and coils. METHODS: Fourteen clips and six coils were scanned in a phantom model with DECT at 100 and 150SnkVp. Four datasets were reconstructed: non-corrected images (filtered-back projection), iterative MAR, VME from DECT at 120 keV, and combined iterative MAR + VME images. Artifact severity scores and visibility of simulated, contrast-filled, adjacent vessels were assessed qualitatively and quantitatively by two independent, blinded readers. RESULTS: Iterative MAR, VME, and combined iterative MAR + VME resulted in a significant reduction of qualitative (p < 0.001) and quantitative clip artifacts (p < 0.005) and improved the visibility of adjacent vessels (p < 0.05) compared to non-corrected images, with lowest artifact scores found in combined iterative MAR + VME images. Titanium clips demonstrated less artifacts than Phynox clips (p < 0.05), and artifact scores increased with clip size. Coil artifacts increased with coil size but were reducible when applying iterative MAR + VME compared to non-corrected images. However, no technique improved the severe artifacts from large, densely packed coils. CONCLUSIONS: Combining iterative MAR with VME allows for an improved metal artifact reduction from clips and smaller, loosely packed coils. Limited value was found for large and densely packed coils.

Blood oxygen-level dependent functional assessment of cerebrovascular reactivity: Feasibility for intraoperative 3 Tesla MRI.

PURPOSE: To assess the feasibility of functional blood oxygen-level dependent (BOLD) MRI to evaluate intraoperative cerebrovascular reactivity (CVR) at 3 Tesla field strength. METHODS: Ten consecutive neurosurgical subjects scheduled for a clinical intraoperative MRI examination were enrolled in this study. In addition to the clinical protocol a BOLD sequence was implemented with three cycles of 44 s apnea to calculate CVR values on a voxel-by-voxel basis throughout the brain. The CVR range was then color-coded and superimposed on an anatomical volume to create high spatial resolution CVR maps. RESULTS: Ten subjects (mean age 34.8 ± 13.4; 2 females) uneventfully underwent the intraoperative BOLD protocol, with no complications occurring. Whole-brain CVR for all subjects was (mean ± SD) 0.69 ± 0.42, whereas CVR was markedly higher for tumor subjects as compared to vascular subjects, 0.81 ± 0.44 versus 0.33 ± 0.10, respectively. Furthermore, color-coded functional maps could be robustly interpreted for a whole-brain assessment of CVR. CONCLUSION: We demonstrate that intraoperative BOLD MRI is feasible in creating functional maps to assess cerebrovascular reactivity throughout the brain in subjects undergoing a neurosurgical procedure. Magn Reson Med 77:806-813, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Dual-Energy Computed Tomography in Stroke Imaging: Technical and Clinical Considerations of Virtual Noncontrast Images for Detection of the Hyperdense Artery Sign.

OBJECTIVE: The technical feasibility of virtual noncontrast (VNC) images from dual-energy computed tomography (DECT) for the detection of the hyperdense artery sign (HAS) in ischemic stroke patients was investigated. METHODS: True noncontrast (TNC) scans of 60 patients either with or without HAS (n = 30 each) were investigated. Clot presence and characteristics were assessed on VNC images from DECT angiography and compared with TNC images. Clot characterization included the level of confidence for diagnosing HAS, a qualitative clot burden score, and quantitative attenuation (Hounsfield unit [HU]) measurements. RESULTS: Sensitivity, specificity, and accuracy of VNC for diagnosing HAS were 97%, 90%, and 93%, respectively. No significant differences were found regarding the diagnostic confidence (P = 0.18) and clot burden score (P = 0.071). No significant HU differences were found among vessels with HAS in VNC (56 ± 7HU) and TNC (57 ± 8HU) (P = 0.691) images. CONCLUSIONS: Virtual noncontrast images derived from DECT enable an accurate detection and characterization of HAS.

Is there a role for conventional MRI and MR diffusion-weighted imaging for distinction of skull base chordoma and chondrosarcoma?

BACKGROUND: Chordoma and chondrosarcoma are locally invasive skull base tumors with similar clinical symptoms and anatomic imaging features as reported in the literature. PURPOSE: To determine differentiation of chordoma and chondrosarcoma of the skull base with conventional magnetic resonance imaging (cMRI) and diffusion-weighted MR imaging (DWI) in comparison to histopathological diagnosis. MATERIAL AND METHODS: This retrospective study comprised 96 (chordoma, n = 64; chondrosarcoma, n = 32) patients with skull base tumors referred to the Paul Scherrer Institute (PSI) for proton therapy. cMRI signal intensities of all tumors were investigated. In addition, median apparent diffusion coefficient (ADC) values were measured in a subgroup of 19 patients (chordoma, n = 11; chondrosarcoma, n = 8). RESULTS: The majority 81.2% (26/32) of chondrosarcomas displayed an off-midline growth pattern, 18.8% (6/32) showed clival invasion, 18.8% (6/32) were located more centrally. Only 4.7% (3/64) of chordomas revealed a lateral clival origin. Using cMRI no significant differences in MR signal intensities were observed in contrast to significantly different ADC values (subgroup of 19/96 patients examined by DWI), with the highest mean value of 2017.2 × 10(-6 )mm(2)/s (SD, 139.9( )mm(2)/s) for chondrosarcoma and significantly lower value of 1263.5 × 10(-6 )mm(2)/s (SD, 100.2 × 10(-6 )mm(2)/s) for chordoma (P = 0.001/median test). CONCLUSION: An off-midline growth pattern can differentiate chondrosarcoma from chordoma on cMRI in a majority of patients. Additional DWI is a promising tool for the differentiation of these skull base tumors.

Pituitary surgery and volumetric assessment of extent of resection: a paradigm shift in the use of intraoperative magnetic resonance imaging.

OBJECTIVE: The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas. METHODS: Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS. The quantitative contribution of 3T-iMRI was measured as a percentage of the additional rate of GTR and of the EOR achieved after 3T-iMRI. RESULTS: The cohort consisted of 50 patients (51 operations) harboring 33 nonfunctioning and 18 functioning pituitary adenomas. Mean adenoma diameter and volume were 21.1 mm (range 5-47 mm) and 5.23 cm(3) (range 0.09-22.14 cm(3)), respectively. According to Knosp's classification, 10 cases were Grade 0; 8, Grade 1; 17, Grade 2; 12, Grade 3; and 4, Grade 4. Gross-total resection was the surgical goal (targeted [t]GTR) in 34 of 51 operations and was initially achieved in 16 (47%) of 34 at 3T-iMRI and in 30 (88%) of 34 cases after further resection. In this subgroup, the EOR increased from 91% at 3T-iMRI to 99% at the 3-month MRI (p < 0.05). In the 17 cases in which subtotal resection (STR) had been planned (tSTR), the EOR increased from 79% to 86% (p < 0.05) and GTR could be achieved in 1 case. Intrasellar remnants were present in 20 of 51 procedures at 3T-iMRI and in only 5 (10%) of 51 procedures after further resection (median volume 0.15 cm(3)). Overall, the use of 3T-iMRI led to further resection in 27 (53%) of 51 procedures and permitted GTR in 15 (56%) of these 27 procedures; thus, the GTR rate in the entire cohort increased from 31% (16 of 51) to 61% (31 of 51) and the EOR increased from 87% to 95% (p < 0.05). CONCLUSIONS: The use of high-definition 3T-iMRI allowed precise visualization and quantification of adenoma remnant volume. It helped to increase GTR and EOR rates in both tGTR and tSTR patient groups. Moreover, it helped to achieve low rates of intrasellar remnants. These data support the use of 3T-iMRI to achieve maximal, safe adenoma resection.

The recurrent artery of Heubner in routine selective cerebral angiography.

INTRODUCTION: Heubner's recurrent artery (RAH) in brain selective catheter angiograms (digital subtraction angiography, DSA) was evaluated. METHODS: Bilateral cerebral angiograms with antero-posterior, lateral and oblique frontal views were obtained in 100 neurological patients aged from 5 to 90 years. Site of origin, type of course and branching of the RAH were studied. Three groups were obtained: arteries with solely the horizontal segment visible, horizontal and vertical segments visible and horizontal and vertical with intraparenchymal branches visible. RESULTS: A total of 24 RAHs were recognised in 20 patients: 7 arose from the A1, 5 from the anterior cerebral artery (ACA)-anterior communicating artery (Acom), 11 from the A2, whereas in 1 case, the segment of origin from the ACA could not be identified. Seventeen arteries arose from the lateral wall of the ACA and seven from the superior wall of the A1 segment of the ACA. The RAH was bilaterally seen in 3 patients and unilaterally in 17 with one double RAH. Five RAHs were visible only after contrast injection in the contralateral internal carotid artery. A horizontal segment was visible in 7 arteries, a horizontal followed by a vertical segment without visible intraparenchymal branching pattern was seen in 6 and a horizontal and vertical segment with visible intraparenchymal branching pattern was seen in 11. In five, the artery made a half loop with an inferior-convex curve just before the vertical segment, and in two cases, a full loop was observed. CONCLUSION: The RAH was recognised in 12% of the hemispheres of the present series of neurological patients studied with DSA.

Manipulation of cortical gray matter oxygenation by hyperoxic respiratory challenge: field dependence of R(2) * and MR signal response.

The aim of this study was to quantitatively assess the field strength dependence of the transverse relaxation rate (R(2) *) change in cortical gray matter induced by hyperoxia and hyperoxic hypercapnia versus normoxia in an intra-individual comparison of young healthy volunteers. Medical air (21% O(2) ), pure oxygen and carbogen (95% O(2) , 5% CO(2) ) were alternatively administered in a block-design temporal pattern to induce normoxia, hyperoxia and hyperoxic hypercapnia, respectively. Local R(2) * values were determined from three-dimensional, multiple, radiofrequency-spoiled, fast field echo data acquired at 1.5, 3 and 7 T. Image quality was good at all field strengths. Under normoxia, the mean gray matter R(2) * values were 13.3 ± 2.7 s(-1) (1.5 T), 16.9 ± 0.9 s(-1) (3 T) and 29.0 ± 2.6 s(-1) (7 T). Both hyperoxic gases induced relaxation rate decreases ΔR(2) *, whose magnitudes increased quadratically with the field strength [carbogen: -0.69 ± 0.20 s(-1) (1.5 T), -1.49 ± 0.49 s(-1) (3 T), -5.64 ± 0.67 s(-1) (7 T); oxygen: -0.39 ± 0.20 s(-1) (1.5 T), -0.78 ± 0.48 s(-1) (3 T), -3.86 ± 1.00 s(-1) (7 T)]. Carbogen produced larger R(2) * changes than oxygen at all field strengths. The relative change ΔR(2) */R(2) * also increased with the field strength with a power between 1 and 2 for both carbogen and oxygen. The statistical significance of the R(2) * response improved with increasing B(0) and was higher for carbogen than for oxygen. For a sequence with pure T(2) * weighting of the signal response to respiratory challenge, the results suggested a maximum carbogen-induced signal difference of 19.3% of the baseline signal at 7 T and TE = 38 ms, but a maximum oxygen-induced signal difference of only 3.0% at 1.5 T and TE = 76 ms. For 3 T, maximum signal changes of 4.7% (oxygen) and 8.9% (carbogen) were computed. In conclusion, the R(2) * response to hyperoxic respiratory challenge was stronger for carbogen than for oxygen, and increased quadratically with the static magnetic field strength for both challenges, which highlights the importance of high field strengths for future studies aimed at probing oxygen physiology in clinical settings.

Transvascular in vivo microscopy of the subarachnoid space.

BACKGROUND: The micro-architectonics of the subarachnoid space (SAS) remain partially understood and largely ignored, likely the result of the inability to image these structures in vivo. We explored transvascular imaging with high-frequency optical coherence tomography (HF-OCT) to interrogate the SAS. METHODS: In vivo HF-OCT was performed in 10 dogs in both the posterior and anterior cerebral circulations. The conduit vessels used were the basilar, anterior spinal, and middle and anterior cerebral arteries through which the perivascular SAS was imaged. The HF-OCT imaging probe was introduced via a microcatheter and images were acquired using a contrast injection (3.5 mL/s) for blood clearance. Segmentation and three-dimensional rendering of HF-OCT images were performed to study the different configurations and porosity of the subarachnoid trabeculae (SAT) as a function of location. RESULTS: Of 13 acquisitions, three were excluded due to suboptimal image quality. Analysis of 15 locations from seven animals was performed showing six distinct configurations of arachnoid structures in the posterior circulation and middle cerebral artery, ranging from minimal presence of SAT to dense networks and membranes. Different locations showed predilection for specific arachnoid morphologies. At the basilar bifurcation, a thick, fenestrated membrane had a unique morphology. SAT average thickness was 100 µm and did not vary significantly based on location. Similarly, the porosity of the SAT averaged 91% and showed low variability. CONCLUSION: We have demonstrated the feasibility to image the structures of the SAS with transvascular HF-OCT. Future studies are planned to further map the SAT to increase our understanding of their function and possible impact on neurovascular pathologies.

Patterned Vascularization of Embryonic Mouse Forebrain, and Neuromeric Topology of Major Human Subarachnoidal Arterial Branches: A Prosomeric Mapping.

The prosomeric brain model contemplates progressive regionalization of the central nervous system (CNS) from a molecular and morphological ontogenetic perspective. It defines the forebrain axis relative to the notochord, and contemplates intersecting longitudinal (zonal, columnar) and transversal (neuromeric) patterning mechanisms. A checkboard pattern of histogenetic units of the neural wall results, where each unit is differentially fated by an unique profile of active genes. These natural neural units later expand their radial dimension during neurogenesis, histogenesis, and correlative differential morphogenesis. This fundamental topologic framework is shared by all vertebrates, as a Bauplan, each lineage varying in some subtle aspects. So far the prosomeric model has been applied only to neural structures, but we attempt here a prosomeric analysis of the hypothesis that major vessels invade the brain wall in patterns that are congruent with its intrinsic natural developmental units, as postulated in the prosomeric model. Anatomic and embryologic studies of brain blood vessels have classically recorded a conserved pattern of branches (thus the conventional terminology), and clinical experience has discovered a standard topography of many brain arterial terminal fields. Such results were described under assumptions of the columnar model of the forebrain, prevalent during the last century, but this is found insufficient in depth and explanatory power in the modern molecular scenario. We have thus explored the possibility that brain vascularization in rodents and humans may relate systematically to genoarchitectonic forebrain subdivisions contemplated in the prosomeric model. Specifically, we examined first whether early vascular invasion of some molecularly characterized prosomeric domains shows heterochrony. We indeed found a heterochronic pattern of vascular invasion that distinguishes between adjacent brain areas with differential molecular profiles. We next mapped topologically on the prosomeric model the major arterial branches serving the human brain. The results of this approach bear on the possibility of a developmentally-based modern arterial terminology.

The voxel-wise analysis of false negative fMRI activation in regions of provoked impaired cerebrovascular reactivity.

Task-evoked Blood-oxygenation-level-dependent (BOLD-fMRI) signal activation is widely used to interrogate eloquence of brain areas. However, data interpretation can be improved, especially in regions with absent BOLD-fMRI signal activation. Absent BOLD-fMRI signal activation may actually represent false-negative activation due to impaired cerebrovascular reactivity (BOLD-CVR) of the vascular bed. The relationship between impaired BOLD-CVR and BOLD-fMRI signal activation may be better studied in healthy subjects where neurovascular coupling is known to be intact. Using a model-based prospective end-tidal carbon dioxide (CO2) targeting algorithm, we performed two controlled 3 tesla BOLD-CVR studies on 17 healthy subjects: 1: at the subjects' individual resting end-tidal CO2 baseline. 2: Around +6.0 mmHg CO2 above the subjects' individual resting baseline. Two BOLD-fMRI finger-tapping experiments were performed at similar normo- and hypercapnic levels. Relative BOLD fMRI signal activation and t-values were calculated for BOLD-CVR and BOLD-fMRI data. For each component of the cerebral motor-network (precentral gyrus, postcentral gyrus, supplementary motor area, cerebellum und fronto-operculum), the correlation between BOLD-CVR and BOLD-fMRI signal changes and t-values was investigated. Finally, a voxel-wise quantitative analysis of the impact of BOLD-CVR on BOLD-fMRI was performed. For the motor-network, the linear correlation coefficient between BOLD-CVR and BOLD-fMRI t-values were significant (p<0.01) and in the range 0.33-0.55, similar to the correlations between the CVR and fMRI Δ%signal (p<0.05; range 0.34-0.60). The linear relationship between CVR and fMRI is challenged by our voxel-wise analysis of Δ%signal and t-value change between normo- and hypercapnia. Our main finding is that BOLD fMRI signal activation maps are markedly dampened in the presence of impaired BOLD-CVR and highlights the importance of a complementary BOLD-CVR assessment in addition to a task-evoked BOLD fMRI to identify brain areas at risk for false-negative BOLD-fMRI signal activation.

Diffuse gliomas exhibit whole brain impaired cerebrovascular reactivity.

PURPOSE: Cerebral diffuse gliomas exhibit perilesional impaired cerebrovascular reactivity (CVR), yet the degree of impairment as well as its full spatial extent in the brain remains unknown. With quantitative fMRI, we studied twelve subjects with untreated brain diffuse glioma and twelve healthy controls to assess CVR impairment and determine its distribution throughout the brain. METHODS: In a prospective case-control study, quantitative CVR measurements were derived from BOLD fMRI volumes during standardized iso-oxic changes in carbon dioxide. Whole brain CVR was assessed with additional detailed analyses using specific tumor and tissue masks and compared to datasets of healthy controls. RESULTS: Whole brain CVR was significantly impaired compared to healthy controls (0.11±0.10 versus 0.28±0.8, p<0.01). All diffuse glioma patients exhibited even more severely impaired intralesional CVR (mean 0.01±0.06). Increasing tumor volume significantly correlated with severity of intralesional CVR impairment (p<0.05, R2=0.38), and whole brain CVR impairment (p<0.05, R2=0.55). CONCLUSION: Patients with brain diffuse glioma exhibit intralesional and whole brain impaired CVR with severity correlating to tumor volume. Quantitative fMRI may be entertained to study antitumor therapy efficacy by tracking CVR changes and may have a complementary role to better interpret BOLD associated neurovascular uncoupling.

BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis.

OBJECTIVE: To study blood oxygen level-dependent cerebrovascular reactivity (BOLD-CVR) as a surrogate imaging marker for crossed cerebellar diaschisis (CCD). METHODS: Twenty-five participants with symptomatic unilateral cerebrovascular steno-occlusive disease underwent a BOLD-CVR and an acetazolamide challenged (15O)-H2O-PET study. CCD and cerebellar asymmetry index were determined from PET and compared to BOLD-CVR quantitative values. Neurologic status at admission and outcome after 3 months were determined with NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores. RESULTS: For both the BOLD-CVR and PET examination, a significant cerebellar asymmetry index was found for participants exhibiting CCD (CCD+ vs CCD-: for BOLD-CVR 13.11 ± 9.46 vs 1.52 ± 4.97, p < 0.001; and for PET 7.31 ± 2.75 vs 1.68 ± 2.98, p < 0.001). The area under the curve for BOLD-CVR was 0.89 (95% confidence interval: 0.75-1.0) with 0.91 sensitivity and 0.81 specificity to detect CCD. Participants exhibiting CCD were in poorer clinical condition at baseline (CCD+ vs CCD-: NIHSS 7 vs 1, p = 0.003; mRS 3 vs 1, p = 0.001) and after 3-month follow-up (NIHSS 2 vs 0, p = 0.02; mRS 1 vs 0, p = 0.04). Worse performance on both scores showed an agreement with a larger BOLD-CVR cerebellar asymmetry index. This was not found for PET. CONCLUSIONS: BOLD-CVR demonstrates similar sensitivity to detect CCD as compared to (15O)-H2O-PET in patients with symptomatic unilateral cerebrovascular steno-occlusive disease. Furthermore, participants exhibiting CCD had a poorer baseline neurologic performance and neurologic outcome at 3 months. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that BOLD-CVR identifies CCD in patients with symptomatic unilateral cerebrovascular steno-occlusive disease.

Impact of baseline CO2 on Blood-Oxygenation-Level-Dependent MRI measurements of cerebrovascular reactivity and task-evoked signal activation.

Neurovascular coupling describes the cascade between neuronal activity and subsequent Blood-Oxygenation-Level-Dependent (BOLD) signal increase. Based on this premise, the correlation of this BOLD signal increase with a particular task, such as finger-tapping, is used to map neuronal activation. This signal increase may be dampened in brain areas exhibiting impaired cerebrovascular reactivity (BOLD-CVR), leading to false negative activation. Blood-oxygenation-level-dependent (BOLD) cerebrovascular reactivity (CVR) has also been used to optimize task evoked BOLD signal changes. To measure BOLD-CVR, controlled BOLD-CVR studies have commonly been performed using a preset isocapnic carbon dioxide (CO2; ~40 mmHg) baseline, independent of subjects' resting CO2. This arbitrary baseline, however, may influence BOLD-CVR measurements. We therefore performed BOLD-CVR, as well as BOLD fMRI during a controlled bilateral finger-tapping task in two groups of ten subjects: group A at subject's resting CO2 and group B at a preset isocapnic CO2 baseline (40 mmHg). Whole brain BOLD-CVR was significantly decreased for group B (group A 0.26 (SD 0.05) vs group B 0.16 (SD 0.05), p < 0.001). For the predefined hand area in the precentral cortex, BOLD-CVR and BOLD fMRI signal changes were significantly lower for group B (group A 0.20 (SD 0.04) vs group B 0.13 (SD 0.05), p < 0.01; 1.19 (SD 0.31) vs 0.62 (SD 0.37), p < 0.01).CO2 levels significantly influence both BOLD-CVR and BOLD fMRI measurements. Hence, for an accurate interpretation, baseline CO2 levels and BOLD CVR should be considered complementary to task evoked BOLD fMRI.

Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition.

OBJECTIVE: To improve quantitative cerebrovascular reactivity (CVR) measurements and CO 2 arrival times, we present an iterative analysis capable of decomposing different temporal components of the dynamic carbon dioxide- Blood Oxygen-Level Dependent (CO 2-BOLD) relationship. EXPERIMENTAL DESIGN: Decomposition of the dynamic parameters included a redefinition of the voxel-wise CO 2 arrival time, and a separation from the vascular response to a stepwise increase in CO 2 (Delay to signal Plateau - DTP) and a decrease in CO 2 (Delay to signal Baseline -DTB). Twenty-five (normal) datasets, obtained from BOLD MRI combined with a standardized pseudo-square wave CO 2 change, were co-registered to generate reference atlases for the aforementioned dynamic processes to score the voxel-by-voxel deviation probability from normal range. This analysis is further illustrated in two subjects with unilateral carotid artery occlusion using these reference atlases. PRINCIPAL OBSERVATIONS: We have found that our redefined CO 2 arrival time resulted in the best data fit. Additionally, excluding both dynamic BOLD phases (DTP and DTB) resulted in a static CVR, that is maximal response, defined as CVR calculated only over a normocapnic and hypercapnic calibrated plateau. CONCLUSION: Decomposition and novel iterative modeling of different temporal components of the dynamic CO 2-BOLD relationship improves quantitative CVR measurements.

Modified Dual-Energy Algorithm for Calcified Plaque Removal: Evaluation in Carotid Computed Tomography Angiography and Comparison With Digital Subtraction Angiography.

OBJECTIVES: Computed tomography angiography (CTA) is a valuable tool for the assessment of carotid artery stenosis. However, blooming artifacts from calcified plaques might result in an overestimation of the stenosis grade. The aim of this study was to investigate a new dual-energy computed tomography (DECT) technique with a modified 3-material decomposition algorithm for calcium removal in extracranial carotid artery stenosis. MATERIALS AND METHODS: In this retrospective, institutional review board-approved study, 30 calcified carotid plaques in 22 patients (15 men; mean age, 73 ± 10 years) with clinical suspicion of stroke were included. Dual-energy computed tomography image data were obtained using second-generation dual-source CT with tube voltages at 80 and 140Sn kVp. Conventional CTA and virtual noncalcium (VNCa) images using the modified DECT algorithm were reconstructed. By assessing spectral characteristics, the modified DECT algorithm allows for a selective removal of calcium independent of blooming. Two independent and blinded readers evaluated subjective image quality, blooming artifacts, amount of (residual) calcification, and performed stenosis measurements according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Differences were tested using a pairwise sign test. Paired sample t tests with Bonferroni correction (P < 0.017) and Bland-Altman analyses were used to test for differences in carotid stenosis measurements between VNCa and conventional CTA using digital subtraction angiography (DSA) as the standard of reference. RESULTS: Subjective image quality was similar among conventional CTA and VNCa image data sets (P = 0.82), whereas blooming artifacts were significantly reduced in VNCa images compared with conventional CTA (P < 0.001). Residual calcifications in VNCa images were absent in 11 (37%), minor in 12 (40%), medium sized in 2 (7%), and large in 5 (17%) arteries. Stenosis measurements differed significantly between VNCa (mean NASCET stenosis: 27% ± 20%) and conventional CTA images (mean NASCET stenosis: 39% ± 16%; P < 0.001) and between conventional CTA and DSA (23% ± 16%, P < 0.001). No significant differences in stenosis measurements were observed between VNCa and DSA (P = 0.189), with narrow limits of agreement (mean difference ±1.96 standard deviations: -4.7%, -35.1%, and 25.7%). CONCLUSIONS: A modified 3-material decomposition DECT algorithm for calcium removal was introduced, which allows for an accurate removal of calcified carotid plaques in extracranial carotid artery disease. The algorithm might overcome the problem of overestimation of calcified stenosis due to blooming artifacts in conventional CTA.