Hybrid dynamic bright and black blood angiography by non-contrast-enhanced vessel selective saturation angiography.

The integrity of vessel walls and changes in blood flow are involved in many diseases, and information about these anatomical and physiological conditions is important for a diagnosis. There are several different angiography methods that can be used to generate images for diagnostic purposes, but often using different imaging techniques and MR sequences. The purpose of this study was to develop a method that allows time-resolved, vessel-selective simultaneous bright and black blood imaging by vesselselective blood saturation. Measurements in six volunteers were performed to evaluate the time-resolved bright blood angiography and the significance of the generated black blood contrast. It was shown that this method can be used to generate a black blood contrast with a sufficient signal difference to the surrounding gray matter in addition to the time-resolved and vessel-selective bright blood contrast. Using post-processing methods, whole brain angiograms can be calculated from the acquired data.

Detection of Spinal Cord Multiple Sclerosis Lesions Using a 3D-PSIR Sequence at 1.5 T.

PURPOSE: Multiple sclerosis (MS) is a prevalent autoimmune inflammatory disease. Besides cerebral manifestations, an affection of the spinal cord is typical; however, imaging of the spinal cord is difficult due to its anatomy. The aim of this study was to assess the diagnostic value of a 3D PSIR pulse sequencing at a 1.5 T magnetic field strength for both the cervical and thoracic spinal cord. METHODS: Phase sensitive inversion recovery (PSIR), short tau inversion recovery (STIR) and T2-weighted (T2-w) images of the spinal cord of 50 patients were separately evaluated by three radiologists concerning the number and location of MS lesions. Furthermore, lesion to cord contrast ratios were determined for the cervical and thoracic spinal cord. RESULTS: Of the lesions 54.81% were located in the cervical spinal cord, 42.26% in the thoracic spinal cord and 2.93% in the conus medullaris. The PSIR images showed a higher sensitivity for lesion detection in the cervical and thoracic spinal cord (77.10% and 72.61%, respectively) compared to the STIR images (58.63% and 59.10%, respectively) and the T2-w images (59.95% and 59.52%, respectively). The average lesion to cord contrast ratio was significantly higher in the PSIR images compared to the STIR images (p < 0.001) and the T2-w images (p < 0.001). CONCLUSION: Evaluation of the spinal cord with a 3D PSIR sequence at a magnetic field strength of 1.5 T is feasible with a high sensitivity for the detection of spinal MS lesions for the cervical as well as the thoracic segments. In combination with other pulse sequences it might become a valuable addition in an advanced imaging protocol.

Clinical Value of Using Heart Rate Variability Biofeedback Before Elective CT Coronary Angiography to Reduce Heart Rate and the Need for Beta-Blockers.

The value of biofeedback before elective coronary computed tomography angiography (CCTA) to reduce patients' heart rates (HR) was investigated in the current work. Sixty patients who received CCTA to exclude coronary artery disease were included in our study and separated into two groups: with biofeedback (W-BF) and without biofeedback (WO-BF). The W-BF group used a biofeedback device for 15 min before CCTA. HR was determined in each patient at four measurement time points (MTP): during the pre-examination interview (MTP1), positioning on the CT patient table before CCTA (MTP2), during CCTA image acquisition (MTP3), and after completing CCTA (MTP4). If necessary, beta-blockers were administered in both groups after MTP2 until a HR of less than 65 bpm was achieved. Two board-certified radiologists subsequently assessed the image quality and analyzed the findings. Overall, the need for beta-blockers was significantly lower in patients in the W-BF group than the WO-BF group (p = 0.032). In patients with a HR of 81-90, beta-blockers were not required in four of six cases in the W-BF group, whereas in the WO-BF group all patients needed beta-blockers (p = 0.03). The amount of HR reduction between MTP1 and MTP2 was significantly higher in the W-BF compared to the WO-BF group (p = 0.028). There was no significant difference between the W-BF and WO-BF groups regarding image quality (p = 0.179). By using biofeedback prior to elective CCTA, beta-blocker use could be decreased without compromising CT image quality and analysis, especially in patients with an initial HR of 81-90 bpm.

Frequency of deep-seated cerebral microbleeds in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy.

Background: Cerebral amyloid angiopathy (CAA) is a common disease and the most common cause of lobar hemorrhages in the elderly. Usually, deep-seated microhemorrhages preclude the diagnosis of CAA. In this study, we sought to estimate the frequency of deep-seated microbleeds on MRI in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy. In addition, we describe a cohort of patients with cortical and deep-seated microbleeds on MRI and a histopathological specimen available from lobar hematoma evacuation. Methods: Retrospective database search for histopathological specimens from lobar hematoma evacuation and review of imaging findings (CT and MRI) and patient charts was performed. Results: Between 1 January 2012 and 31 December 2020, 88 specimens from 88 patients were available. A total of 56 specimens were excluded (no brain tissue in the specimen n = 4, other diagnosis n = 8, no MRI n = 43, and no BOLD-based sequence n = 1). Of the remaining 32 patients, 25 patients (78%) did not harbor deep-seated lesions on MRI, of which 17 patients had histopathological features of CAA. A total of seven patients harbored deep-seated CMB. Of these seven patients, three (3/20, 15%) had histopathological features of CAA. Conclusion: Approximately 15% of patients with histopathologically diagnosed CAA harbor deep-seated microbleeds. This finding may add to the discussion on how to identify patients with CAA and deep-seated CMB.

Magnetic resonance imaging of human variegated squirrel bornavirus 1 (VSBV-1) encephalitis reveals diagnostic pattern indistinguishable from Borna disease virus 1 (BoDV-1) encephalitis but typical for bornaviruses.

Human bornavirus encephalitis is an emerging disease caused by the variegated squirrel bornavirus 1 (VSBV-1) and the Borna disease virus 1 (BoDV-1). While characteristic brain magnetic resonance imaging (MRI) changes have been described for BoDV-1 encephalitis, only scarce diagnostic data in VSBV-1 encephalitis exist. We systematically analysed brain MRI scans from all known VSBV-1 encephalitis patients. Initial and follow-up scans demonstrated characteristic T2 hyperintense lesions in the limbic system and the basal ganglia, followed by the brainstem. No involvement of the cerebellar cortex was seen. Deep white matter affection occurred in a later stage of the disease. Strict symmetry of pathologic changes was seen in 62%. T2 hyperintense areas were often associated with low T1 signal intensity and with mass effect. Sinusitis in three patients on the first MRI and an early involvement of the limbic system suggest an olfactory route of VSBV-1 entry. The viral spread could occur per continuitatem to adjacent anatomical brain regions or along specific neural tracts to more distant brain regions. The number and extent of lesions did not correlate with the length of patients' survivals. The overall pattern closely resembles that described for BoDV-1 encephalitis. The exact bornavirus species can thus not be deduced from imaging results alone, and molecular testing and serology should be performed to confirm the causative bornavirus. As VSBV-1 is likely of tropical origin, and MRI investigations are increasingly available globally, imaging techniques might be helpful to facilitate an early presumptive diagnosis of VSBV-1 encephalitis when molecular and/or serological testing is not available.

Intratumoral Distribution of Lactate and the Monocarboxylate Transporters 1 and 4 in Human Glioblastoma Multiforme and Their Relationships to Tumor Progression-Associated Markers.

(1) Background: Metabolic reprogramming has been postulated to be one of the hallmarks of cancer, thus representing a promising therapeutic target also in glioblastoma multiforme (GBM). Hypoxic tumor cells produce lactate, and monocarboxylate transporters (MCTs) play an important role in its distribution; (2) Methods: We examined the distribution of lactate by multi voxel magnetic resonance spectroscopic imaging and ELISA in glioblastoma multiforme (GBM) patients. In addition, we investigated the expression and cellular localization of MCT1, MCT4, and of several markers connected to tumor progression by quantitative PCR and immunofluorescence double-staining in human GBM ex vivo tissues; (3) Results: The highest lactate concentration was found at the center of the vital parts of the tumor. Three main GBM groups could be distinguished according to their regional gene expression differences of the investigated genes. MCT1 and MCT4 were found on cells undergoing epithelial to mesenchymal transition and on tumor stem-like cells. GBM cells revealing an expression of cellular dormancy markers, showed positive staining for MCT4; (4) Conclusion: Our findings indicate the existence of individual differences in the regional distribution of MCT1 and MCT4 and suggest that both transporters have distinct connections to GBM progression processes, which could contribute to the drug resistance of MCT-inhibitors.

Non-contrast enhanced molecular characterization of C6 rat glioma tumor at 7 T.

PURPOSE: The aim of this study was to investigate, how to assess the relevant magnetization changes in the rat brain tissue due to the present of glioma tumor and its growth at a 7 T animal magnetic resonance imaging (MRI) system. MATERIAL AND METHODS: For this study, a custom-built two dimensional (2D) chemical exchange saturation transfer (CEST) pulse sequence was optimized for different tissue properties using fresh and cooked quail eggs. C6 tumor cells were investigated by in-vivo and post-mortem measurements in six Wistar rats using the optimized CEST sequence up to 5 weeks. Magnetization transfer ratio (MTR)- and asymmetric MTR (MTRasym)-maps of rat brains were created at different frequency offsets. In-vivo results were verified by 1H spectroscopic, histological and also in-vitro C6 cell culture examinations. RESULTS: The CEST module for the optimal visualization of magnetization effects consists of five RF-pulses, each with a duration of 20 ms and a flip angle of 180°. In-vivo and post-mortem z-spectra of the cerebrospinal fluid (CSF), cortex, myelinated/demyelinated, healthy and tumorous tissue and tumor rim were obtained. The magnetization level and shape of the z-spectra on the upfield and downfield from the water peak were not the same. The magnetization dips on the upfield and downfield from the water peak of the z-spectra disappeared due to the thermal denaturation in cooked quail eggs and due to formaldehyde-induced fixation in post-mortem rat brains. The z-spectra of the rat brain in a range of ±2 to ±4 ppm displayed valuable information about the differentiation of various brain regions from the tumor tissue. Histological examinations confirmed our results. The C6 cell culture examinations showed that the observed magnetization changes in the rat brain occurred only due to the interaction between glioma cells and their environment in the rat brain and not from the C6 tumor cells. CONCLUSIONS: Based on our in-vivo and post-mortem results, it is to be recommended to create the MTR-maps at a special offset frequency depending on the aim of research project instead of MTRasym-maps. Otherwise, the desired effect attenuates or vanishes.

Automated versus manual imaging assessment of early ischemic changes in acute stroke: comparison of two software packages and expert consensus.

AIM: The purpose of our study was to compare the agreement of both the total Alberta Stroke Program Early CT Score (ASPECTS) and region-based scores from two automated ASPECTS software packages and an expert consensus (EC) reading with final ASPECTS in a selected cohort of patients who had prompt reperfusion from endovascular thrombectomy (EVT). METHODS: ASPECTS were retrospectively and blindly assessed by two software packages and EC on baseline non-contrast-enhanced computed tomography (NCCT) images. All patients had multimodal CT imaging including NCCT, CT angiography, and CT perfusion which demonstrated an acute anterior circulation ischemic stroke with a large vessel occlusion. Final ASPECTS on follow-up scans in patients who had EVT and achieved complete reperfusion within 100 min from NCCT served as ground truth and were compared to total and region-based scores. RESULTS: Fifty-two patients met our study criteria. Moderate agreement was obtained between both software packages and EC for total ASPECTS and there was no significant difference in overall performance. However, the software packages differed with respect to regional contribution. In this cohort, the majority of infarcted regions were deep structures. Package A was more sensitive in cortical areas than the other methods, but at a cost of specificity. EC and software package B had greater sensitivity, but lower specificity for deep brain structures. CONCLUSION: In this cohort, using the final ASPECTS as ground truth, no clinically significant difference was observed for total ASPECT score between human or automated packages, but there were differences in the characteristics of the regions scored. KEY POINTS: • Some national stroke guidelines have incorporated ASPECTS in their recommendations for selecting patients for endovascular therapy. • Computer-aided diagnosis is a promising tool to aid the evaluation of early ischemic changes identified on CT. • Software packages for automated ASPECTS assessment differed significantly with respect to regional contribution without any significant difference in the overall ASPECT score.

Optimization of 3D phase contrast venography for the assessment of the cranio-cervical venous system at 1.5 T.

PURPOSE: The aim of this work was to optimize a three-dimensional (3D) phase-contrast venography (PCV) product MR pulse sequence in order to obtain clinically reliable images with less artifacts for an improved depiction of the cranio-cervical venous vessels. METHODS: Starting from the product sequence, the 3D PCV protocol was optimized in eight steps with respect to the velocity encoding (Venc) direction and value, slice thickness, reduction of susceptibility artifacts and arterial contamination, gradient mode and radio-frequency (RF)-spoiling, B0-Shimming, asymmetric echo technique and RF-pulse type, and flip angle. The product and optimized protocol was used to perform 3D PCV in 12 healthy male volunteers with a median age of 50 years using a state-of-the-art 1.5-T MR system. For evaluation, the cranio-cervical venous system was divided into 15 segments. These segments were evaluated by three radiologists with experience in neuroradiology. An ordinal scoring system was used to access the overall diagnostic quality, arterial contamination, and the quality of visualization. RESULTS: Image quality in the optimized 3D PCV was graded as "excellent" by all readers in 65.3% of the cases (p < 0.0001). The visualization of venous segments was strongly improved: it was considered diagnostic in 81.8% of all cases using the optimized sequence and in 47.6% for the product 3D PCV (p < 0.0001), respectively. The optimized protocol improved the imaging of all venous segments (p < 0.0001). CONCLUSION: The optimized 3D PCV pulse sequence showed superior results compared to the product 3D PCV for the visualization and evaluation of the venous system in all healthy volunteers.

Occupation-Associated Fatal Limbic Encephalitis Caused by Variegated Squirrel Bornavirus 1, Germany, 2013.

Limbic encephalitis is commonly regarded as an autoimmune-mediated disease. However, after the recent detection of zoonotic variegated squirrel bornavirus 1 in a Prevost's squirrel (Callosciurus prevostii) in a zoo in northern Germany, we retrospectively investigated a fatal case in an autoantibody-seronegative animal caretaker who had worked at that zoo. The virus had been discovered in 2015 as the cause of a cluster of cases of fatal encephalitis among breeders of variegated squirrels (Sciurus variegatoides) in eastern Germany. Molecular assays and immunohistochemistry detected a limbic distribution of the virus in brain tissue of the animal caretaker. Phylogenetic analyses demonstrated a spillover infection from the Prevost's squirrel. Antibodies against bornaviruses were detected in the patient's cerebrospinal fluid by immunofluorescence and newly developed ELISAs and immunoblot. The putative antigenic epitope was identified on the viral nucleoprotein. Other zoo workers were not infected; however, avoidance of direct contact with exotic squirrels and screening of squirrels are recommended.

MRI in mild pediatric traumatic brain injury: diagnostic overkill or useful tool?

PURPOSE: Magnetic resonance imaging (MRI) is a sensitive imaging tool which lacks the burden of ionizing radiation. It is not established as primary diagnostic tool in traumatic brain injury (TBI). The purpose of this study was to evaluate the usefulness of MRI as initial imaging modality in the emergency management of mild pediatric TBI. METHODS: Children (0-18 years, sub-divided in four age-groups) with mild TBI who received MRI in the emergency department were identified. Clinical characteristics and trauma mechanisms were evaluated retrospectively. Univariate and multivariate logistic regression analyses were used to identify clinical factors that might be indicative for trauma sequelae on MRI scans. RESULTS: An institutional case series of 569 patients (322 male/247 female; age < 18years; (GCS ≥ 13), who received MRI for mild TBI, was analyzed. Multi-sequence imaging (including T2, T2*, FLAIR, and diffusion-weighted sequences) was feasible without sedation in 96.8% of cases (sedation, 1.8%; general anesthesia, 1.4%). MRI revealed trauma-associated findings in 13% of all cases; incidental findings were detected in 4.7%. In our cohort, GCS deterioration, scalp hematoma, clinical signs of skull base fractures, and horseback riding accidents were related to structural trauma sequelae on MRI. CONCLUSIONS: MRI is a practical primary imaging tool for evaluating children with mild TBI in the emergency department. The presented analyses demonstrated that in our institution, MRI imaging is performed frequently in the emergency department. It resulted mostly in normal findings. This may reflect uneasiness of when to perform imaging in mild TBI and appears retrospectively as an "overdo." There are clinical factors that are more likely associated with MRI-positive findings. Their reliability has to be evaluated in prospective studies in order to formulate further decision rules of when to perform MRI imaging or not.

Advanced CT for diagnosis of seizure-related stroke mimics.

BACKGROUND AND PURPOSE: It is assumed that up to 30 % of clinically diagnosed acute ischaemic strokes (AIS) are actually stroke mimics (SM). Our aim was to evaluate the usefulness of advanced CT including CT angiography (CTA) and CT perfusion (CTP) findings when distinguishing AIS from seizure-related SM. METHODS: Over a 22-month period data were gathered of patients who presented to our stroke centre with AIS-like symptoms and were examined immediately with an advanced CT, analysed and evaluated by two experienced neuroradiologists who preferred SM rather than AIS. All these patients additionally received electroencephalography and follow-up imaging. CTA was the important feature to exclude vessel occlusion or haemodynamic relevant stenosis. Perfusion patterns were retrospectively analysed qualitatively. RESULTS: The most common perfusion abnormality was cortical hyperperfusion (22/37 [59.5 %] patients) followed by a hypoperfusion pattern with a cortical-subcortical involvement (15/37 [40.5 %] patients) without evidence of vessel occlusion or stenosis. Seizure-related hyper- and hypoperfusion patterns typically crossed the normal anatomical vascular territories boundaries. CONCLUSION: Beyond its use in core and penumbra estimation, advanced CT provides important information to emergency physicians in the difficult clinical diagnosis when differentiating between AIS and seizure-related symptoms with an important impact on therapeutic decision-making. KEY POINTS: • Advanced CT helps to differentiate between ischaemic strokes and stroke mimics. • Seizure-related perfusion patterns are distinct from ischaemia hypoperfusion. • Advanced CT could improve rapid adequate treatment for AIS and seizure events.

Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.

OBJECTIVES: Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. METHODS: We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. RESULTS: In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. CONCLUSION: Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.

Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy.

BACKGROUND AND PURPOSE: Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy. METHODS: Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke. RESULTS: In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson r for A=0.42, B=0.64, and C=0.83; P<0.001). Bland-Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients. CONCLUSIONS: Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software.