Use of MR signal intensity variations to highlight structures at risk along brain biopsy trajectories.

OBJECTIVE: Postoperative intracerebral hemorrhages are significant complications following brain stereotactic biopsy. They can derive from anatomical structure (sulci, vessels) damage that is missed during stereotactic trajectory planning. In this study, the authors investigated the ability to detect contact between structures at risk and stereotactic trajectories using signal analysis from MRI obtained during clinical practice, with the aim to propose a visual tool to highlight areas with anatomical structures at risk of damage along the biopsy trajectory. METHODS: The authors retrospectively analyzed actual stereotactic trajectories using intraoperative imaging (intraoperative 2D radiographs in the exploratory data set and intraoperative 3D scans in the confirmatory data set). The MR signal variation along each biopsy trajectory was matched with the patient's anatomy. RESULTS: In the exploratory data set (n = 154 patients), 32 contacts between the actual biopsy trajectory and an anatomical structure at risk were identified along 28 (18.2%) biopsy trajectories, corresponding to 8 preventable intracerebral hemorrhages. Variations of the mean derivative of the MR signal intensity were significantly different between trajectories with and without contact (the pathological threshold of the mean derivative of the MR signal intensity was defined as ± 0.030 arbitrary units; p < 0.0001), with a sensitivity of 89.3% and specificity of 74.6% to detect a contact. In the confirmatory data set (n = 73 patients), the sensitivity and specificity of the 0.030 threshold to detect a contact between the actual stereotactic trajectory and an anatomical structure at risk were 81.3% and 68.4%, respectively. CONCLUSIONS: Variations of the mean derivative of the MR signal intensity can be converted into a green/red color code along the planned biopsy trajectory to highlight anatomical structures at risk, which can help neurosurgeons during the surgical planning of stereotactic procedures.

Orbitofrontal sulcal patterns in catatonia.

BACKGROUND: Catatonia is a psychomotor syndrome frequently observed in disorders with neurodevelopmental impairments, including psychiatric disorders such as schizophrenia. The orbitofrontal cortex (OFC) has been repeatedly associated with catatonia. It presents with an important interindividual morphological variability, with three distinct H-shaped sulcal patterns, types I, II, and III, based on the continuity of the medial and lateral orbital sulci. Types II and III have been identified as neurodevelopmental risk factors for schizophrenia. The sulcal pattern of the OFC has never been investigated in catatonia despite the role of the OFC in the pathophysiology and the neurodevelopmental component of catatonia. METHODS: In this context, we performed a retrospective analysis of the OFC sulcal pattern in carefully selected homogeneous and matched subgroups of schizophrenia patients with catatonia (N = 58) or without catatonia (N = 65), and healthy controls (N = 82). RESULTS: Logistic regression analyses revealed a group effect on OFC sulcal pattern in the left (χ2 = 18.1; p < .001) and right (χ2 = 28.3; p < .001) hemispheres. Catatonia patients were found to have more type III and less type I in both hemispheres compared to healthy controls and more type III on the left hemisphere compared to schizophrenia patients without catatonia. CONCLUSION: Because the sulcal patterns are indirect markers of early brain development, our findings support a neurodevelopmental origin of catatonia and may shed light on the pathophysiology of this syndrome.

Feasibility and Accuracy of Robot-Assisted, Stereotactic Biopsy Using 3-Dimensional Intraoperative Imaging and Frameless Registration Tool.

BACKGROUND: Robot-assisted stereotactic biopsy is evolving: 3-dimensional intraoperative imaging tools and new frameless registration systems are spreading. OBJECTIVE: To investigate the accuracy and effectiveness of a new stereotactic biopsy procedure. METHODS: Observational, retrospective analysis of consecutive robot-assisted stereotactic biopsies using the Neurolocate (Renishaw) frameless registration system and intraoperative O-Arm (Medtronic) performed at a single institution in adults (2019-2021) and comparison with a historical series from the same institution (2006-2016) not using the Neurolocate nor the O-Arm. RESULTS: In 100 patients (55% men), 6.2 ± 2.5 (1-14) biopsy samples were obtained at 1.7 ± 0.7 (1-3) biopsy sites. An histomolecular diagnosis was obtained in 96% of cases. The mean duration of the procedure was 59.0 ± 22.3 min. The mean distance between the planned and the actual target was 0.7 ± 0.7 mm. On systematic postoperative computed tomography scans, a hemorrhage ≥10 mm was observed in 8 cases (8%) while pneumocephalus was distant from the biopsy site in 76%. A Karnofsky Performance Status score decrease ≥20 points postoperatively was observed in 4%. The average dose length product was 159.7 ± 63.4 mGy cm. Compared with the historical neurosurgical procedure, this new procedure had similar diagnostic yield (96 vs 98.7%; P = .111) and rate of postoperative disability (4.0 vs 4.2%, P = .914) but was shorter (57.8 ± 22.9 vs 77.8 ± 20.9 min; P < .001) despite older patients. CONCLUSION: Robot-assisted stereotactic biopsy using the Neurolocate frameless registration system and intraoperative O-Arm is a safe and effective neurosurgical procedure. The accuracy of this robot-assisted surgery supports its effectiveness for daily use in stereotactic neurosurgery.

Synthetic FLAIR as a Substitute for FLAIR Sequence in Acute Ischemic Stroke.

Background In acute ischemic stroke (AIS), fluid-attenuated inversion recovery (FLAIR) is used for treatment decisions when onset time is unknown. Synthetic FLAIR could be generated with deep learning from information embedded in diffusion-weighted imaging (DWI) and could replace acquired FLAIR sequence (real FLAIR) and shorten MRI duration. Purpose To compare performance of synthetic and real FLAIR for DWI-FLAIR mismatch estimation and identification of patients presenting within 4.5 hours from symptom onset. Materials and Methods In this retrospective study, all pretreatment and early follow-up (<48 hours after symptom onset) MRI data sets including DWI (b = 0-1000 sec/mm2) and FLAIR sequences obtained in consecutive patients with AIS referred for reperfusion therapies between January 2002 and May 2019 were included. On the training set (80%), a generative adversarial network was trained to produce synthetic FLAIR with DWI as input. On the test set (20%), synthetic FLAIR was computed without real FLAIR knowledge. The DWI-FLAIR mismatch was evaluated on both FLAIR data sets by four independent readers. Interobserver reproducibility and DWI-FLAIR mismatch concordance between synthetic and real FLAIR were evaluated with κ statistics. Sensitivity and specificity for identification of AIS within 4.5 hours were compared in patients with known onset time by using McNemar test. Results The study included 1416 MRI scans (861 patients; median age, 71 years [interquartile range, 57-81 years]; 375 men), yielding 1134 and 282 scans for training and test sets, respectively. Regarding DWI-FLAIR mismatch, interobserver reproducibility was substantial for real and synthetic FLAIR (κ = 0.80 [95% CI: 0.74, 0.87] and 0.80 [95% CI: 0.74, 0.87], respectively). After consensus, concordance between real and synthetic FLAIR was almost perfect (κ = 0.88; 95% CI: 0.82, 0.93). Diagnostic value for identifying AIS within 4.5 hours did not differ between real and synthetic FLAIR (sensitivity: 107 of 131 [82%] vs 111 of 131 [85%], P = .2; specificity: 96 of 104 [92%] vs 96 of 104 [92%], respectively, P > .99). Conclusion Synthetic fluid-attenuated inversion recovery (FLAIR) had diagnostic performances similar to real FLAIR in depicting diffusion-weighted imaging-FLAIR mismatch and in helping to identify early acute ischemic stroke, and it may accelerate MRI protocols. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Carroll and Hurley in this issue.

Dependency of R2 and R2 * relaxation on Gd-DTPA concentration in arterial blood: Influence of hematocrit and magnetic field strength.

Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R2(*) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time-consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R2(*) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open-source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient-echo sequence (proof-of-concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient-echo and spin-echo sequences. The results show that for both gradient-echo and spin-echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R2(*) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion.

Cranioplastic Surgery and Acclimation Training for Awake Mouse fMRI.

MRI is a promising tool for translational research to link brain function and structure in animal models of disease to patients with neuropsychiatric disorders. However, given that mouse functional MRI (fMRI) typically relies on anesthetics to suppress head motion and physiological noise, it has been difficult to directly compare brain fMRI in anesthetized mice with that in conscious patients. Here, we developed a new system to acquire fMRI in awake mice, which includes a head positioner and dedicated radio frequency coil. The system was used to investigate functional brain networks in conscious mice, with the goal of enabling future studies to bridge fMRI of disease model animals with human fMRI. Cranioplastic surgery was performed to affix the head mount and the cupped-hand handling method was performed to minimize stress during MRI scanning. Here we describe the new mouse fMRI system, cranioplastic surgery and acclimation protocol. Graphic abstract: Awake fMRI system to investigate the neuronal activity in awaked mice.

Postoperative intracerebral haematomas following stereotactic biopsies: Poor planning or poor execution?

BACKGROUND: Postoperative intracerebral haematomas represent a serious complication following stereotactic biopsy. We investigated the possible underlying causes - poor planning or poor execution - of postoperative intracerebral haematomas following stereotactic biopsies. METHODS: We performed a technical investigation using a retrospective single-centre consecutive series of robot-assisted stereotactic biopsies for a supratentorial diffuse glioma in adults. Each actual biopsy trajectory was reviewed to search for a conflict with an anatomical structure at risk. RESULTS: From 379 patients, 12 (3.2%) presented with a postoperative intracerebral haematoma ≥20 mm on postoperative CT-scan (3 requiring surgical evacuation); 11 of them had available intraoperative imaging (bi-planar stereoscopic teleangiography x-rays at each biopsy site). The actual biopsy trajectory was similar to the planned biopsy trajectory in these 11 cases. In 72.7% (8/11) of these cases, the actual biopsy trajectory was found to contact a structure at risk (blood vessel and cerebral sulcus) and identified as the intracerebral haematoma origin. CONCLUSIONS: Robot-assisted stereotactic biopsy is an accurate procedure. Postoperative intracerebral haematomas mainly derive from human-related errors during trajectory planning.

fMRI detects bilateral brain network activation following unilateral chemogenetic activation of direct striatal projection neurons.

Abnormal structural and functional connectivity in the striatum during neurological disorders has been reported using functional magnetic resonance imaging (fMRI), although the effects of cell-type specific neuronal stimulation on fMRI and related behavioral alterations are not well understood. In this study, we combined DREADD technology with fMRI ("chemo-fMRI") to investigate alterations of spontaneous neuronal activity. These were induced by the unilateral activation of dopamine D1 receptor-expressing neurons (D1-neurons) in the mouse dorsal striatum (DS). After clozapine (CLZ) stimulation of the excitatory DREADD expressed in D1-neurons, the fractional amplitude of low frequency fluctuations (fALFF) increased bilaterally in the medial thalamus, nucleus accumbens and cortex. In addition, we found that the gamma-band of local field potentials was increased in the stimulated DS and cortex bilaterally. These results provide insights for better interpretation of cell type-specific activity changes in fMRI.

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and diffusion fMRI responses in mouse visual cortex.

The contribution of astrocytes to the BOLD fMRI and DfMRI responses in visual cortex of mice following visual stimulation was investigated using TGN-020, an aquaporin 4 (AQP4) channel blocker, acting as an astrocyte function perturbator. Under TGN-020 injection the amplitude of the BOLD fMRI response became significantly higher. In contrast no significant changes in the DfMRI responses and the electrophysiological responses were observed. Those results further confirm the implications of astrocytes in the neurovascular coupling mechanism underlying BOLD fMRI, but not in the DfMRI responses which remained unsensitive to astrocyte function perturbation.

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor.

The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its dysfunction might lead to several brain pathologies, including the Alzheimer's disease. A key component of the GS and brain tissue water circulation is the astrocyte which is regulated by acquaporin-4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo and non-invasively.

Awake functional MRI detects neural circuit dysfunction in a mouse model of autism.

MRI has potential as a translational approach from rodents to humans. However, given that mouse functional MRI (fMRI) uses anesthetics for suppression of motion, it has been difficult to directly compare the result of fMRI in "unconsciousness" disease model mice with that in "consciousness" patients. We develop awake fMRI to investigate brain function in 15q dup mice, a copy number variation model of autism. Compared to wild-type mice, we find that 15q dup is associated with whole-brain functional hypoconnectivity and diminished fMRI responses to odors of stranger mice. Ex vivo diffusion MRI reveals widespread anomalies in white matter ultrastructure in 15q dup mice, suggesting a putative anatomical substrate for these functional hypoconnectivity. We show that d-cycloserine (DCS) treatment partially normalizes these anormalies in the frontal cortex of 15q dup mice and rescues some social behaviors. Our results demonstrate the utility of awake rodent fMRI and provide a rationale for further investigation of DCS therapy.

Interpulse phase corrections for unbalanced pseudo-continuous arterial spin labeling at high magnetic field.

PURPOSE: To evaluate a prescan-based radiofrequency phase-correction strategy for unbalanced pseudo-continuous arterial spin labeling (pCASL) at 9.4 T in vivo and to test its robustness toward suboptimal shim conditions. METHODS: Label and control interpulse phases were optimized separately by means of two prescans in rats. The mean perfusion as well as the interhemispherical symmetry were measured for several phase combinations (optimized versus theoretical phases) to evaluate the correction quality. Interpulse phases were also optimized under degraded shim conditions (i.e., up to four times the study shim values) to test the strategy's robustness. RESULTS: For all tested shim conditions, the full arterial spin labeling (ASL) signal could be restored. Without any correction, the relative ASL signal was 1.4 ± 1.7%. It increased to 3.6 ± 1.4% with an optimized label phase and to 5.3 ± 1.2% with optimized label and control phases. Moreover, asymmetry between brain hemispheres, which could be as high as 100% without phase optimization, was dramatically reduced to 1 ± 3% when applying optimized label and control phases. CONCLUSIONS: Pseudo-continuous ASL at high magnetic field is very sensitive to shim conditions. Label and control radiofrequency phase optimization based on prescans robustly maximizes the ASL signal obtained with unbalanced pCASL and minimizes the asymmetry between hemispheres. Magn Reson Med 79:1314-1324, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Application of calibrated fMRI in Alzheimer's disease.

Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO2). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials. In the present work, we applied a calibrated fMRI approach referred to as Quantitative O2 (QUO2) in a cohort of probable AD dementia and age-matched control participants. The resulting CBF, OEF and CMRO2 values fell within the range from previous studies using positron emission tomography (PET) with 15O labeling. Moreover, the typical parietotemporal pattern of hypoperfusion and hypometabolism in AD was observed, especially in the precuneus, a particularly vulnerable region. We detected no deficit in frontal CBF, nor in whole grey matter CVR, which supports the hypothesis that the effects observed were associated specifically with AD rather than generalized vascular disease. Some key pitfalls affecting both ASL and BOLD methods were encountered, such as prolonged arterial transit times (particularly in the occipital lobe), the presence of susceptibility artifacts obscuring medial temporal regions, and the challenges associated with the hypercapnic manipulation in AD patients and elderly participants. The present results are encouraging and demonstrate the promise of calibrated fMRI measurements as potential biomarkers in AD. Although CMRO2 can be imaged with 15O PET, the QUO2 method uses more widely available imaging infrastructure, avoids exposure to ionizing radiation, and integrates with other MRI-based measures of brain structure and function.

Impact of tissue T1 on perfusion measurement with arterial spin labeling.

PURPOSE: Arterial spin labeling (ASL) may provide quantitative maps of cerebral blood flow (CBF). Because labeled water exchanges with tissue water, this study evaluates the influence of tissue T1 on CBF quantification using ASL. METHODS: To locally modify T1 , a low dose of manganese (Mn) was intracerebrally injected in one hemisphere of 19 rats (cortex or striatum). Tissue T1 and CBF were mapped using inversion recovery and continuous ASL experiments at 4.7T. RESULTS: Mn reduced the tissue T1 by more than 30% but had little impact on other tissue properties as assessed via dynamic susceptibility and diffusion MRI. Using a single-compartment model, the use of a single tissue T1 value yielded a mean relative ipsilateral (Mn-injected) to contralateral (noninjected) CBF difference of -34% in cortex and -22% in striatum tissue. With a T1 map, these values became -7% and +8%, respectively. CONCLUSION: A low dose of Mn reduces the tissue T1 without modifying CBF. Heterogeneous T1 impacts the ASL estimate of CBF in a region-dependent way. In animals, and when T1 modifications exceed the accuracy with which the tissue T1 can be determined, an estimate of tissue T1 should be obtained when quantifying CBF with an ASL technique. Magn Reson Med 77:1656-1664, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Microvascular MRI and unsupervised clustering yields histology-resembling images in two rat models of glioma.

Imaging heterogeneous cancer lesions is a real challenge. For diagnosis, histology often remains the reference, but it is widely acknowledged that biopsies are not reliable. There is thus a strong interest in establishing a link between clinical in vivo imaging and the biologic properties of tissues. In this study, we propose to construct histology-resembling images based on tissue microvascularization, a magnetic resonance imaging (MRI) accessible source of contrast. To integrate the large amount of information collected with microvascular MRI, we combined a manual delineation of a spatial region of interest with an unsupervised, model-based cluster analysis (Mclust). This approach was applied to two rat models of glioma (C6 and F98). Six MRI parameters were mapped: apparent diffusion coefficient, vessel wall permeability, cerebral blood volume fraction, cerebral blood flow, tissular oxygen saturation, and cerebral metabolic rate of oxygen. Five clusters, defined by their MRI features, were found to correspond to specific histologic features, and revealed intratumoral spatial structures. These results suggest that the presence of a cluster within a tumor can be used to assess the presence of a tissue type. In addition, the cluster composition, i.e., a signature of the intratumoral structure, could be used to characterize tumor models as histology does.

Neuronal transport defects of the MAP6 KO mouse - a model of schizophrenia - and alleviation by Epothilone D treatment, as observed using MEMRI.

The MAP6 (microtubule-associated protein 6) KO mouse is a microtubule-deficient model of schizophrenia that exhibits severe behavioral disorders that are associated with synaptic plasticity anomalies. These defects are alleviated not only by neuroleptics, which are the gold standard molecules for the treatment of schizophrenia, but also by Epothilone D (Epo D), which is a microtubule-stabilizing molecule. To compare the neuronal transport between MAP6 KO and wild-type mice and to measure the effect of Epo D treatment on neuronal transport in KO mice, MnCl2 was injected in the primary somatosensory cortex. Then, using manganese-enhanced magnetic resonance imaging (MEMRI), we followed the propagation of Mn(2+) through axonal tracts and brain regions that are connected to the somatosensory cortex. In MAP6 KO mice, the measure of the MRI relative signal intensity over 24h revealed that the Mn(2+) transport rate was affected with a stronger effect on long-range and polysynaptic connections than in short-range and monosynaptic tracts. The chronic treatment of MAP6 KO mice with Epo D strongly increased Mn(2+) propagation within both mono- and polysynaptic connections. Our results clearly indicate an in vivo deficit in neuronal Mn(2+) transport in KO MAP6 mice, which might be due to both axonal transport defects and synaptic transmission impairments. Epo D treatment alleviated the axonal transport defects, and this improvement most likely contributes to the positive effect of Epo D on behavioral defects in KO MAP6 mice.

A simulation tool for dynamic contrast enhanced MRI.

The quantification of bolus-tracking MRI techniques remains challenging. The acquisition usually relies on one contrast and the analysis on a simplified model of the various phenomena that arise within a voxel, leading to inaccurate perfusion estimates. To evaluate how simplifications in the interstitial model impact perfusion estimates, we propose a numerical tool to simulate the MR signal provided by a dynamic contrast enhanced (DCE) MRI experiment. Our model encompasses the intrinsic R1 and R2 relaxations, the magnetic field perturbations induced by susceptibility interfaces (vessels and cells), the diffusion of the water protons, the blood flow, the permeability of the vessel wall to the the contrast agent (CA) and the constrained diffusion of the CA within the voxel. The blood compartment is modeled as a uniform compartment. The different blocks of the simulation are validated and compared to classical models. The impact of the CA diffusivity on the permeability and blood volume estimates is evaluated. Simulations demonstrate that the CA diffusivity slightly impacts the permeability estimates (< 5% for classical blood flow and CA diffusion). The effect of long echo times is investigated. Simulations show that DCE-MRI performed with an echo time TE = 5 ms may already lead to significant underestimation of the blood volume (up to 30% lower for brain tumor permeability values). The potential and the versatility of the proposed implementation are evaluated by running the simulation with realistic vascular geometry obtained from two photons microscopy and with impermeable cells in the extravascular environment. In conclusion, the proposed simulation tool describes DCE-MRI experiments and may be used to evaluate and optimize acquisition and processing strategies.