Patrick M. Heiler

Two‐dimensional radial acquisition technique with density adaption in sodium MRI

Conventional 2D radial projections suffer from losses in signal‐to‐noise ratio efficiency because of the nonuniform k‐space sampling. In this study, a 2D projection reconstruction method with variable gradient amplitudes is presented to cover the k‐space uniformly. The gradient is designed to keep the average sampling density constant. By this, signal‐to‐noise ratio is increased, and the linear form of the radial trajectory is kept. The simple gradient design and low hardware requirements in respect of slew rate allow an easy implementation at MR scanners. Measurements with the density‐adapted 2D radial trajectory were compared with the conventional projection reconstruction method. It is demonstrated that the density‐adapted 2D radial trajectory technique provides higher signal‐to‐noise ratio (up to 28% in brain tissue), less blurring, and fewer artifacts in the presence of magnetic field inhomogeneities than imaging with the conventional 2D radial trajectory scheme. The presented sequence is well‐suited for electrocardiographically gated sodium heart MRI and other applications with short relaxation times. Magn Reson Med, 2010.

In vivo 39K, 23Na and 1H MR imaging using a triple resonant RF coil setup

The maintenance of a gradient of potassium and sodium ions across the cell membranes is essential for the physiological function of the mammal organism. The measurement of the spatial distribution of pathologically changing ion concentrations of (23)Na and (39)K with magnetic resonance imaging offers a promising approach in clinical diagnostics to measure tissue viability. Existing studies were focused mainly on (23)Na imaging as well as spectroscopy with only one post-mortem study for (39)K imaging. In this paper a triple resonant RF coil setup for the rat head at 9.4T is presented for imaging of both nuclei ((23)Na and (39)K) and the acquisition of anatomical proton images in the same experiment without moving the subject or the RF coil. In vivo MR images of (39)K and (23)Na in the rat brain were acquired as well as anatomical proton images in the same scanning session.

Chemical shift sodium imaging in a mouse model of thromboembolic stroke at 9.4 T

To estimate changes in the 23Na density and in the 23Na relaxation time T2* in the anatomically small murine brain after stroke.

Thrombolysis in Experimental Cerebral Amyloid Angiopathy and the Risk of Secondary Intracerebral Hemorrhage

Background and Purpose— Intracerebral hemorrhage (ICH) is the most adverse event of thrombolysis in ischemic stroke. Cerebral amyloid angiopathy increases the risk for spontaneous lobar ICH. Although thrombolysis may be performed in cerebral amyloid angiopathy–affected patients, there is still little knowledge available on the risk for secondary ICH. Methods— We investigated the effect of recombinant tissue-type plasminogen activator on experimental ischemic stroke in APP23 transgenic mice (n=18) and wild-type littermates (n=15). Focal ischemic stroke was induced in 26-month-old mice by temporal middle cerebral artery occlusion (filament model), followed by treatment with 10 mg/kg recombinant tissue-type plasminogen activator. Twenty-four hours later, a functional score was assessed and the mice were euthanized for histological analysis. ICH was classified as grades 1 to 3 depending on severity. Results— The groups did not differ regarding mortality (P=0.67) and functional deficit (P=0.18). Compared with wild-type mice, the APP23 genotype was associated with a higher appearance for ICH in the infarct area (P=0.05). ICH severity grades 2 and 3 correlated significantly with infarct size (P=0.004 and 0.008, respectively). Conclusions— The APP23 genotype was not associated with increased mortality or worse functional outcome. Our results suggest an increased risk for ICH in the cerebral amyloid angiopathy–affected brain; however, no ICH was observed outside the ischemic area.

Increased BOLD sensitivity in the orbitofrontal cortex using slice-dependent echo times at 3 T☆

Functional magnetic resonance imaging (fMRI) exploits the blood oxygenation level dependent (BOLD) effect to detect neuronal activation related to various experimental paradigms. Some of these, such as reversal learning, involve the orbitofrontal cortex and its interaction with other brain regions like the amygdala, striatum or dorsolateral prefrontal cortex. These paradigms are commonly investigated with event-related methods and gradient echo-planar imaging (EPI) with short echo time of 27 ms. However, susceptibility-induced signal losses and image distortions in the orbitofrontal cortex are still a problem for this optimized sequence as this brain region consists of several slices with different optimal echo times. An EPI sequence with slice-dependent echo times is suitable to maximize BOLD sensitivity in all slices and might thus improve signal detection in the orbitofrontal cortex. To test this hypothesis, we first optimized echo times via BOLD sensitivity simulation. Second, we measured 12 healthy volunteers using a standard EPI sequence with an echo time of 27 ms and a modified EPI sequence with echo times ranging from 22 ms to 47 ms. In the orbitofrontal cortex, the number of activated voxels increased from 87 ± 44 to 549 ± 83 and the maximal t-value increased from 4.4 ± 0.3 to 5.4 ± 0.3 when the modified EPI was used. We conclude that an EPI with slice-dependent echo times may be a valuable tool to mitigate susceptibility artifacts in event-related whole-brain fMRI studies with a focus on the orbitofrontal cortex.

Development of cerebral microbleeds in the APP23-transgenic mouse model of cerebral amyloid angiopathy - a 9.4 Tesla MRI study

Background: Cerebral amyloid angiopathy (CAA) is characterized by extracellular deposition of amyloid β (Aβ) around cerebral arteries and capillaries and leads to an increased risk for vascular dementia, spontaneous lobar hemorrhage, convexal subarachnoid hemorrhage, and transient focal neurological episodes, which might be an indicator of imminent spontaneous intracerebral hemorrhage. In CAA cerebral microbleeds (cMBs) with a cortical/juxtacortical distribution are frequently observed in standard magnetic resonance imaging (MRI). In vivo MRI of transgenic mouse models of CAA may serve as a useful tool to investigate translational aspects of the disease. Materials and Methods: APP23-transgenic mice demonstrate cerebrovascular Aβ deposition with subsequent neuropathological changes characteristic for CAA. We performed a 9.4 Tesla high field MRI study using T2, T2* and time of flight-magnetic resonance angiograpy (TOF-MRA) sequences in APP23-transgenic mice and wildtype (wt) littermates at the age of 8, 12, 16, 20 and 24 months, respectively. Numbers, size, and location of cMBs are reported. Results: T2* imaging demonstrated cMBs (diameter 50–300 μm) located in the neocortex and, to a lesser degree, in the thalamus. cMBs were detected at the earliest at 16 months of age. Numbers increased exponentially with age, with 2.5 ± 2 (median ± interquartilrange) at 16 months, 15 ± 6 at 20 months, and 31.5 ± 17 at 24 months of age, respectively. Conclusion: We report the temporal and spatial development of cMBs in the aging APP23-transgenic mouse model which develops characteristic pathological patterns known from human CAA. We expect this mouse model to serve as a useful tool to non-invasively monitor mid- and longterm translational aspects of CAA and to investigate experimental therapeutic strategies in longitudinal studies.

Artifact free T2*-weighted imaging at high spatial resolution using segmented EPI sequences

The aim of this work was the development of novel measurement techniques that acquire high resolution T2*-weighted datasets in measurement times as short as possible without suffering from noticeable blurring and ghosting artifacts. Therefore, two new measurement techniques were developed that acquire a smoother k-space than generic multi shot echo planar imaging sequences. One is based on the principle of echo train shifting, the other on the reversed gradient method. Simulations and phantom measurements demonstrate that echo train shifting works properly and reduces artifacts in multi shot echo planar imaging. For maximum SNR-efficiency this technique was further improved by adding a second contrast. Both contrasts can be acquired within a prolongation in measurement time by a factor of 1.5, leading to an SNR increase by approximately 2. Furthermore it is demonstrated that the reversed gradient method remarkably reduces artifacts caused by a discontinuous k-space weighting. Assuming sequence parameters as feasible for fMRI experiments, artifact free T2*-weighted images with a matrix size of 256 × 256 leading to an in-plane resolution in the submillimeter range can be obtained in about 2s per slice.

Thromboembolic stroke in C57BL/6 mice monitored by 9.4 T MRI using a 1H cryo probe

BackgroundA new thromboembolic animal model showed beneficial effects of t-PA with an infarct volume reduction of 36.8% in swiss mice. Because knock-out animal experiments for stroke frequently used C57BL76 mice we evaluated t-PA effects in this mouse strain and measured infarct volume and vascular recanalisation in-vivo by using high-field 9.4 T MRI and a 1H surface cryo coil.MethodsClot formation was triggered by microinjection of murine thrombin into the right middle cerebral artery (MCA). Animals (n = 28) were treated with 10 mg/kg, 5 mg/kg or no tissue plasminogen activator (t-PA) 40 min after MCA occlusion. For MR-imaging a Bruker 9.4 T animal system with a 1H surface cryo probe was used and a T2-weighted RARE sequence, a diffusion weighted multishot EPI sequence and a 3D flow-compensated gradient echo TOF angiography were performed.ResultsThe infarct volume in animals treated with t-PA was significantly reduced (0.67 ± 1.38 mm3 for 10 mg/kg and 10.9 ± 8.79 mm3 for 5 mg/kg vs. 19.76 ± 2.72 mm3 ; p < 0.001) compared to untreated mice. An additional group was reperfused with t-PA inside the MRI. Already ten minutes after beginning of t-PA treatment, reperfusion flow was re-established in the right MCA. However, signal intensity was lower than in the contralateral MCA. This reduction in cerebral blood flow was attenuated during the first 60 minutes after reperfusion. 24 h after MCA occlusion and reperfusion, no difference in signal intensity of the contralateral and ipsilateral MCAs was observed.ConclusionsWe confirm a t-Pa effect using this stroke model in the C57BL76 mouse strain and demonstrate a chronological sequence MRI imaging after t-PA using a 1H surface cryo coil in a 9.4 T MRI. This setting will allow testing of new thrombolytic strategies for stroke treatment in-vivo in C57BL76 knock-out mice.

Statin Therapy and the Development of Cerebral Amyloid Angiopathy--A Rodent in Vivo Approach.

Background: Cerebral amyloid angiopathy (CAA) is characterized by vascular deposition of amyloid β (Aβ) with a higher incidence of cerebral microbleeds (cMBs) and spontaneous hemorrhage. Since statins are known for their benefit in vascular disease we tested for the effect on CAA. Methods: APP23-transgenic mice received atorvastatin-supplemented food starting at the age of eight months (n = 13), 12 months (n = 7), and 16 months (n = 6), respectively. Controls (n = 16) received standard food only. At 24 months of age cMBs were determined with T2*-weighted 9.4T magnetic resonance imaging and graded by size. Results: Control mice displayed an average of 35 ± 18.5 cMBs (mean ± standard deviation), compared to 29.3 ± 9.8 in mice with eight months (p = 0.49), 24.9 ± 21.3 with 12 months (p = 0.26), and 27.8 ± 15.4 with 16 months of atorvastatin treatment (p = 0.27). In combined analysis treated mice showed lower absolute numbers (27.4 ± 15.6, p = 0.16) compared to controls and also after adjustment for cMB size (p = 0.13). Conclusion: Despite to a non-significant trend towards fewer cMBs our results failed to provide evidence for beneficial effects of long-term atorvastatin treatment in the APP23-transgenic mouse model of CAA. A higher risk for bleeding complications was not observed.