Jan Sedlacik

Susceptibility weighted imaging at ultra high magnetic field strengths: Theoretical considerations and experimental results

We present numerical simulations and experimental results for susceptibility weighted imaging (SWI) at 7 T. Magnitude, phase, and SWI contrast were simulated for different voxel geometries and imaging parameters, resulting in an echo time of 14 msec for optimum contrast between veins and surrounding tissue. Slice thickness of twice the in‐plane voxel size or more resulted in optimum vessel visibility. Phantom and in vivo data are in very good agreement with the simulations and the delineation of vessels at 7 T was superior compared to lower field strengths. The phase of the complex data reveals anatomical details that are complementary to the corresponding magnitude images. Susceptibility weighted imaging at very high field strengths is a promising technique because of its high sensitivity to tissue susceptibility, its low specific absorption rate, and the phases negligible sensitivity to B1 inhomogeneities. Magn Reson Med 60:1155–1168, 2008.

Nonnvasive assessment of vascular architecture and function during modulated blood oxygenation using susceptibility weighted magnetic resonance imaging.

Susceptibility weighted imaging (SWI) is a BOLD‐sensitive method for visualizing anatomical features such as small cerebral veins in high detail. The purpose of this study was to evaluate high‐resolution SWI in combination with a modulation of blood oxygenation by breathing of air, carbogen, and oxygen and to directly visualize the effects of changing blood oxygenation on the magnetic field inside and around venous blood vessels. Signal changes associated with the response to carbogen and oxygen breathing were evaluated in different anatomic regions in healthy volunteers and in two patients with brain tumors. In the magnitude images inhalation of carbogen led to significant signal intensity changes ranging from +4.4 ± 1.9% to +9.5 ± 1.4% in gray matter and no significant changes in thalamus, putamen, and white matter. During oxygen breathing mean signal changes were smaller than during carbogen breathing. The method is capable of producing high‐resolution functional maps of BOLD response to carbogen and oxygen breathing as well as high‐resolution images of venous vasculature. Its sensitivity to changes in blood oxygenation was demonstrated by in vivo visualization of the BOLD effect via phase imaging. Magn Reson Med 54:87–95, 2005.

ToF-SWI: simultaneous time of flight and fully flow compensated susceptibility weighted imaging.

To perform systematic investigations on parameter selection of a dual‐echo sequence (ToF‐SWI) for combined 3D time‐of‐flight (ToF) angiography and susceptibility weighted imaging (SWI).

Investigation of the influence of carbon dioxide concentrations on cerebral physiology by susceptibility-weighted magnetic resonance imaging (SWI).

Breathing carbogen (5% CO2 / 95% O2) dramatically increases cerebral blood flow (CBF), which induces a blood oxygenation level dependent (BOLD) related vascular signal change due to the concomitantly increased oxyhemoglobin concentration in the veins. However, carbogen often causes discomfort due to its forced strong and deep breathing which also may lead to severe motion artifacts in magnetic resonance imaging. In this study, susceptibility-weighted imaging (SWI) was performed with CO2 levels of 0, 1.67%, 3.33% and 5% to measure the induced BOLD signal changes in venous vessels and brain tissue. Susceptibility-weighted imaging data from 15 healthy subjects and one patient with a brain tumor were acquired. The signal magnitude of cortical veins increased relative to pure oxygen by 3.5+/-3.8%, 10.3+/-4.5%, and 22.7+/-8.8% for CO2 concentrations of 1.67%, 3.33%, and 5%, respectively. Significant signal changes were detected in segmented white matter for 5% CO2, and gray matter for both 3.3% and 5% CO2. The influence of motion artifacts was clearly traceable by the broadening of the signal distribution in segmented tissue. Heterogeneous signal changes were observed in the patient for the same tumor regions at both 3.33% and 5% CO2. Signal phase values of white and gray matter changed only very slightly with increasing CO2. Based on our findings we recommend the reduction of CO2 concentration to about 3% when using a mixture of O2 and CO2. All subjects also reported highly improved breathing comfort at 3.3% CO2 as compared to 5%. The marginal phase change of white and gray matter supports the assumption that deoxygenated blood alone does not explain the commonly observed phase difference between the two tissues.

Intranasal Delivery of Neural Stem/Progenitor Cells: A Noninvasive Passage to Target Intracerebral Glioma

Stem cell‐based therapies for neurological disorders, including brain tumors, advance continuously toward clinical trials. Optimized cell delivery to the central nervous system remains a challenge since direct intracerebral injection is an invasive method with low transplantation efficiency. We investigated the feasibility of intranasal administration of neural stem/progenitor cells (NSPCs) as an alternative, noninvasive, and direct passage for the delivery of stem cells to target malignant gliomas. Tumor‐targeting and migratory pathways of murine and human NSPCs were investigated by intravital magnetic resonance imaging and in histological time course analyses in the intracerebral U87, NCE‐G55T2, and syngenic Gl261 glioblastoma models. Intranasally administered NSPCs displayed a rapid, targeted tumor tropism with significant numbers of NSPCs accumulating specifically at the intracerebral glioma site within 6 hours after intranasal delivery. Histological time series analysis revealed that NSPCs migrated within the first 24 hours mainly via olfactory pathways but also by systemic distribution via the microvasculature of the nasal mucosa. Intranasal application of NSPCs leads to a rapid, targeted migration of cells toward intracerebral gliomas. The directional distribution of cells accumulating intra‐ and peritumorally makes the intranasal delivery of NSPCs a promising noninvasive and convenient alternative delivery method for the treatment of malignant gliomas with the possibility of multiple dosing regimens.

Obtaining blood oxygenation levels from MR signal behavior in the presence of single venous vessels

The MR signal decay in gradient echo sequences includes signal loss due to spin dephasing caused by static magnetic field inhomogeneities. This decay can be calculated for different geometries of the susceptibility distribution, such as spheres, cylinders, or cylinder networks. In particular, the model of an infinitely long cylinder is a good approximation for single straight blood vessels. Blood oxygenation and blood volume fraction are important parameters, which influence the signal in a characteristic way. In this work the signal decays for a single cylindrical vessel were investigated and evaluated in simulations, phantom measurements as well as in vivo measurements of small single veins in the human brain by using a 3D multiecho gradient echo sequence. Good agreement between simulations and phantom experiments was obtained for different experimental settings. Based on the simulations, physiologically consistent values of venous blood oxygenation level, Y, were extracted from the in vivo measurements of different veins and volunteers (Y = 0.55 ± 0.02). The methods ability to measure changes in venous blood oxygenation induced by carbogen breathing was demonstrated in one volunteer, where an increase from Y ≈ 0.5 to Y ≈ 0.7 was observed. Magn Reson Med 58:1035–1044, 2007.

Preclinical models for neuroblastoma: establishing a baseline for treatment.

Background Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system. Principal Findings Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a “standard of care” chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents. Significance The studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer.

Quantitative Diffusion-Weighted and Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging Analysis of T2 Hypointense Lesion Components in Pediatric Diffuse Intrinsic Pontine Glioma

BACKGROUND AND PURPOSE: Focal anaplasia characterized by T2 hypointensity, signal-intensity enhancement on postcontrast T1-weighted MR imaging and restricted water diffusion has been reported in a patient with juvenile pilocytic astrocytoma. We identified T2HOF with these MR imaging characteristics in children with DIPG and hypothesized that these represent areas of focal anaplasia; and may, therefore, have increased perfusion properties and should be characterized by increased perfusion. Thus, we used DSC to investigate our hypothesis. MATERIALS AND METHODS: We retrospectively reviewed the baseline MR imaging scans of 86 patients (49 girls, 37 boys; median age, 6.1 years; range, 1.1–17.6 years) treated for DIPG at our hospital (2004–2009). T2HOF with the described MR imaging characteristics was identified in 10 patients. We used a region of interest−based approach to compare the ADC, FA, rCBV, rCBF, and rMTT of T2HOF with those of the typical T2HRT. RESULTS: The ADC of T2HOF with the specified MR imaging characteristics was significantly lower than that of T2HRT (range, 0.71–1.95 μm2/ms versus 1.36–2.13 μm2/ms; P < .01); and the FA (range, 0.12–0.34 versus 0.07–0.24; P = .03) and rCBV (range, 0.4–2.62 versus 0.23–1.57; P = .01) values of T2HOFs were significantly higher. CONCLUSIONS: Our data suggest that T2HOF in DIPG may represent areas of focal anaplasia and underline the importance of regional, rather than global, tumor-field analysis. T2HOF may be the ideal target when stereotactic biopsy of tumors that present with an inhomogeneous T2 signal intensity is considered.

Investigations on the effect of caffeine on cerebral venous vessel contrast by using susceptibility-weighted imaging (SWI) at 1.5, 3 and 7 T.

Caffeine lowers the blood oxygenation level-dependent (BOLD) signal by acting as an adenosine antagonist, thus decreasing the cerebral blood flow (CBF). The aims of this study were to demonstrate the sensitivity of susceptibility-weighted imaging (SWI) to caffeine-induced changes in CBF and to investigate the time course and magnitude of signal change in caffeine-habituated and -abstinent volunteers. High-resolution susceptibility-weighted images were acquired with both groups at 1.5 T using a fully velocity compensated 3D gradient echo sequence. Following a native scan, subjects were given a tablet containing 200 mg of caffeine. Scans were repeated for about 1 h and the acquired 3D data sets were co-registered to each other. BOLD signal changes of several venous vessels were analyzed in dedicated ROIs. Maps of relative signal change clearly visualized the caffeine-induced signal response of veins. Only very weak signal changes of about -2+/-1% were found in both, grey and white matter and -1+/-2% in the ventricles. Maximum signal decrease of veins occurred 40-50 min after caffeine ingestion. The signal decrease was -16.5+/-6.5% and -22.7+/-8.3% for the caffeine users group and abstainers, respectively. The signal difference of both groups was statistically significant (Students t-test, t=2.16, p=0.021). Data acquired at 1.5, 3 and 7 T with echo times scaled to the respective field strength display very similar temporal signal behavior.

Susceptibility weighted imaging: data acquisition, image reconstruction and clinical applications.

Susceptibility-weighted imaging (SWI) is a novel method, that combines magnitude and phase information from a high-resolution, fully velocity compensated 3D T2-weighted gradient echo sequence. Phase images are unwrapped and high pass filtered to highlight phase changes associated with venous vessels and converted into a mask that is multiplied with the corresponding phase image. This technique has been applied thus far to the imaging of tumors, vascular malformations, trauma, stroke, micro-hemorrhages, and as a functional imaging method. The purpose of this paper is to present an overview of the current status of the technique and to illustrate its potential.