A new framework for assessing subject-specific whole brain circulation and perfusion using MRI-based measurements and a multi-scale continuous flow model

A large variety of severe medical conditions involve alterations in microvascular circulation. Hence, measurements or simulation of circulation and perfusion has considerable clinical value and can be used for diagnostics, evaluation of treatment efficacy, and for surgical planning. However, the accuracy of traditional tracer kinetic one-compartment models is limited due to scale dependency. As a remedy, we propose a scale invariant mathematical framework for simulating whole brain perfusion. The suggested framework is based on a segmentation of anatomical geometry down to imaging voxel resolution. Large vessels in the arterial and venous network are identified from time-of-flight (ToF) and quantitative susceptibility mapping (QSM). Macro-scale flow in the large-vessel-network is accurately modelled using the Hagen-Poiseuille equation, whereas capillary flow is treated as two-compartment porous media flow. Macro-scale flow is coupled with micro-scale flow by a spatially distributing support function in the terminal endings. Perfusion is defined as the transition of fluid from the arterial to the venous compartment. We demonstrate a whole brain simulation of tracer propagation on a realistic geometric model of the human brain, where the model comprises distinct areas of grey and white matter, as well as large vessels in the arterial and venous vascular network. Our proposed framework is an accurate and viable alternative to traditional compartment models, with high relevance for simulation of brain perfusion and also for restoration of field parameters in clinical brain perfusion applications.publishedVersio

Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study

AbstractQuantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance phase images. It is commonly assumed that paramagnetic iron is the predominant source of susceptibility variations in gray matter as many studies have reported a reasonable correlation of magnetic susceptibility with brain iron concentrations in vivo. Instead of performing direct comparisons, however, all these studies used the putative iron concentrations reported in the hallmark study by Hallgren and Sourander (1958) for their analysis. Consequently, the extent to which QSM can serve to reliably assess brain iron levels is not yet fully clear. To provide such information we investigated the relation between bulk tissue magnetic susceptibility and brain iron concentration in unfixed (in situ) post mortem brains of 13 subjects using MRI and inductively coupled plasma mass spectrometry. A strong linear correlation between chemically determined iron concentration and bulk magnetic susceptibility was found in gray matter structures (r=0.84, p<0.001), whereas the correlation coefficient was much lower in white matter (r=0.27, p<0.001). The slope of the overall linear correlation was consistent with theoretical considerations of the magnetism of ferritin supporting that most of the iron in the brain is bound to ferritin proteins. In conclusion, iron is the dominant source of magnetic susceptibility in deep gray matter and can be assessed with QSM. In white matter regions the estimation of iron concentrations by QSM is less accurate and more complex because the counteracting contribution from diamagnetic myelinated neuronal fibers confounds the interpretation

Quantitative susceptibility mapping in ischemic stroke patients after successful recanalization

Quantitative susceptibility mapping (QSM) is a novel processing method for gradient-echo magnetic resonance imaging (MRI). Higher magnetic susceptibility in cortical veins have been observed on susceptibility maps in the ischemic hemisphere of stroke patients, indicating an increased oxygen extraction fraction (OEF). Our goal was to investigate susceptibility in veins of stroke patients after successful recanalization in order to analyze the value of QSM in predicting tissue prognosis and clinical outcome. We analyzed MR images of 23 patients with stroke due to unilateral middle cerebral artery (MCA)-M1/M2 occlusion acquired 24-72 h after successful thrombectomy. The susceptibilities of veins were obtained from QSM and compared between the stroke territory, the ipsilateral non-ischemic MCA territory and the contralateral MCA territory. As outcome variables, early infarct size and functional disability (modified Rankin Scale, mRS) after 3-5 months was used. The median susceptibility value of cortical veins in the ischemic core was 41% lower compared to the ipsilateral non-ischemic MCA territory and 38% lower than on the contralateral MCA territory. Strikingly, in none of the patients prominent vessels with high susceptibility signal were found after recanalization. Venous susceptibility values within the infarct did not correlate with infarct volume or functional disability after 3-5 months. Low venous susceptibility within the infarct core after successful recanalization of the occluded vessel likely indicates poor oxygen extraction arising from tissue damage. We did not identify peri-infarct tissue with increased susceptibility values as potential surrogate of former penumbral areas. We found no correlation of QSM parameters with infarct size or outcome.ISSN:2045-232

Vascular and Tissue Changes of Magnetic Susceptibility in the Mouse Brain After Transient Cerebral Ischemia

Magnetic resonance imaging (MRI) is an important aid for physicians in the diagnosis and management of patients with acute ischemic stroke. Quantitative susceptibility mapping (QSM) has been recently introduced as a novel MRI post-processing technique of gradient recalled echo (GRE) data. QSM yields quantitative maps of the corresponding underlying magnetic susceptibility distribution. QSM is useful for depicting the anatomy and for detecting brain abnormalities. But its utility in the context of ischemic stroke has not been extensively characterized. We tested the ability of QSM to characterize tissue changes in the transient middle cerebral artery occlusion (tMCAO) model of cerebral ischemia. We acquired high resolution GRE of mice brains at different time points after tMCAO for computation of QSM and MR frequency maps, and compared these maps with DWI and multi-slice multi-echo imaging acquired with the same animals. Prominent vessels with increased magnetic susceptibility were visible on frequency and magnetic susceptibility maps surrounding the lesion at all times (mostly visible at >12h after reperfusion). Immunohistological examination revealed compressed capillaries and prominent vessels after reestablishing reperfusion may indicate a compensatory effect. In addition, on both contrast maps regions of decreased magnetic susceptibility delineated at 24h and 48h after reperfusion that were distinctly different from the lesions seen on maps of the apparent diffusion coefficient (ADC) and T2 relaxation time constant. Since QSM can be performed without additional acquisition time in the course of acute stroke MRI examination, it may provide complementary information for the diagnostic follow-up of cerebral ischemia

Improved elimination of phase effects from background field inhomogeneities for susceptibility weighted imaging at high magnetic field strengths

To enhance susceptibility-related contrast of magnetic resonance images, the phase of susceptibility weighted data needs to be corrected for background inhomogeneities and phase wraps caused by them. Current methods either use homodyne filtering or a combination of phase unwrapping and high pass filtering. The drawback of homodyne filtering is incomplete elimination of phase wraps in areas with steep phase topography produced by background inhomogeneities of the static magnetic field. The disadvantage of phase unwrapping is that it requires subsequent high pass filtering, which introduces artifacts in areas with very steep transitions, such as areas near interfaces between parenchyma and bone or air. A method is proposed that reduces the artifacts associated with high pass filtering without sacrificing the advantages of phase unwrapping. This technique is demonstrated with phantom data at 1.5 T and with human data at 1.5, 3 and 7 T

A new framework for assessing subject-specific whole brain circulation and perfusion using MRI-based measurements and a multi-scale continuous flow model

A large variety of severe medical conditions involve alterations in microvascular circulation. Hence, measurements or simulation of circulation and perfusion has considerable clinical value and can be used for diagnostics, evaluation of treatment efficacy, and for surgical planning. However, the accuracy of traditional tracer kinetic one-compartment models is limited due to scale dependency. As a remedy, we propose a scale invariant mathematical framework for simulating whole brain perfusion. The suggested framework is based on a segmentation of anatomical geometry down to imaging voxel resolution. Large vessels in the arterial and venous network are identified from time-of-flight (ToF) and quantitative susceptibility mapping (QSM). Macro-scale flow in the large-vessel-network is accurately modelled using the Hagen-Poiseuille equation, whereas capillary flow is treated as two-compartment porous media flow. Macro-scale flow is coupled with micro-scale flow by a spatially distributing support function in the terminal endings. Perfusion is defined as the transition of fluid from the arterial to the venous compartment. We demonstrate a whole brain simulation of tracer propagation on a realistic geometric model of the human brain, where the model comprises distinct areas of grey and white matter, as well as large vessels in the arterial and venous vascular network. Our proposed framework is an accurate and viable alternative to traditional compartment models, with high relevance for simulation of brain perfusion and also for restoration of field parameters in clinical brain perfusion applications

Radiology Case Reports

Detection of multiple intracranial hemorrhages in a child with acute lymphocytic leukemia (ALL) by susceptibility weighted imaging (SWI

Safety and effectiveness of percutaneous sclerotherapy for venous disorders of the labia majora in patients with vascular malformations

Objective: The aim of this study was to evaluate the safety and clinical outcomes of percutaneous sclerotherapy of venous disorders of the labia majora in patients with vascular malformations of the lower limbs. Methods: Thirty percutaneous sclerotherapy treatments were performed over a 6-year period among 17 female patients with symptomatic venous malformation (VM) or secondary varicosis of the labia majora. Four patients were treated with sclerotherapy alone, 13 patients had additional procedures to control the VM before sclerotherapy. Polidocanol was used as sclerosant. Indications for sclerotherapy included pain, bleeding, thrombophlebitis, and swelling. Genitourinary symptoms were recorded. The number of treatments and procedure-related complications were registered. Complications were classified according to the Society of Interventional Radiology (SIR) classification system (grade A-E). The 3-month postintervention follow-up included magnetic resonance imaging, clinical examination, and a symptom-related questionnaire. If no reintervention was necessary, consultation was scheduled biannually. Results: All patients had local swelling and pain; only a fraction of the patients had further symptoms with bleeding or thrombophlebitis (47% each). Eight patients required reintervention. No major complications were observed; minor complications such as postprocedural swelling occurred in 29% (SIR grade A), pain occurred in 17% (SIR grade B), and skin blistering developed in 5% (SIR grade B). Upon follow-up examination after a median of 40 months, 76% showed complete relief of symptoms, and 23% reported partial relief. All patients reported a substantial reduction in pain (75% >5 points in visual analogue scale) and swelling (88% complete cessation). Conclusions: Percutaneous sclerotherapy is a safe and effective treatment option of VM and secondary varicosis of the labia majora

MR imaging of venous malformations: sciatic nerve infiltration patterns and involved muscle groups

The aim of this retrospective cross-sectional study was to provide an MRI-based examination framework of venous malformations (VMs) infiltrating the sciatic nerve and determine the frequency of nerve infiltration patterns and muscle involvement in correlation to the patients' quality of life. Pelvic and lower limb MR images of 378 patients with vascular malformations were examined retrospectively. Pain levels and restriction of motion were evaluated with a questionnaire. Cross-sectional areas of affected nerves were compared at standardized anatomical landmarks. Intraneural infiltration patterns and involvement of muscles surrounding the sciatic nerve were documented. Sciatic nerve infiltration occurred in 23/299 patients (7.7%) with VM. In all cases (23/23; 100%), gluteal or hamstring muscles surrounding the nerve were affected by the VM. Infiltrated nerves were enlarged and showed signal alterations (T2-hyperintensity) compared to the unaffected side. Enlarged nerve cross-sectional areas were associated with elevated pain levels. Three nerve infiltration patterns were observed: subepineurial (12/23; 52.2%), subparaneurial (6/23; 26.1%) and combined (5/23; 21.7%) infiltration. This study provides a clinically relevant assessment for sciatic nerve infiltration patterns and muscle involvement of VMs, while suggesting that VMs in gluteal and hamstring muscles require closer investigation of the sciatic nerve by the radiologist

Changes of deep gray matter magnetic susceptibility over 2years in multiple sclerosis and healthy control brain

In multiple sclerosis, pathological changes of both tissue iron and myelin occur, yet these factors have not been characterized in a longitudinal fashion using the novel iron- and myelin-sensitive quantitative susceptibility mapping (QSM) MRI technique. We investigated disease-relevant tissue changes associated with myelin loss and iron accumulation in multiple sclerosis deep gray matter (DGM) over two years. One-hundred twenty (120) multiple sclerosis patients and 40 age- and sex-matched healthy controls were included in this prospective study. Written informed consent and local IRB approval were obtained from all participants. Clinical testing and QSM were performed both at baseline and at follow-up. Brain magnetic susceptibility was measured in major DGM structures. Temporal (baseline vs. follow-up) and cross-sectional (multiple sclerosis vs. controls) differences were studied using mixed factorial ANOVA analysis and appropriate t-tests. At either time-point, multiple sclerosis patients had significantly higher susceptibility in the caudate and globus pallidus and lower susceptibility in the thalamus. Over two years, susceptibility increased significantly in the caudate of both controls and multiple sclerosis patients. Inverse thalamic findings among MS patients suggest a multi-phase pathology explained by simultaneous myelin loss and/or iron accumulation followed by iron depletion and/or calcium deposition at later stages. Keywords: Quantitative susceptibility mapping, QSM, Iron, Multiple sclerosis, Longitudinal stud