Sebastian Flacke

Novel MRI Contrast Agent for Molecular Imaging of Fibrin Implications for Detecting Vulnerable Plaques

Background—Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques. Methods and Results—The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd3+ atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL · s−1 · pmol−1 (10% Gd-DTPA nanoparticles) to 0.54 mL · s−1 · pmol−1 for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was ≈118±21, and that between the targeted clot and the control clot was 131±37. Conclusions—These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.

Silent and apparent cerebral embolism after retrograde catheterisation of the aortic valve in valvular stenosis: a prospective, randomised study

BACKGROUND In most patients, severity of valvular aortic stenosis can be accurately assessed non-invasively by echocardiography. However, retrograde catheterisation of the aortic valve is often undertaken. This procedure has a potential risk of neurological complications, with an unknown incidence of clinically silent embolism. We aimed to establish the frequency of clinically apparent and silent cerebral embolism after this procedure. METHODS We prospectively randomised 152 consecutive patients with valvular aortic stenosis at a German university hospital to receive either cardiac catheterisation with (n=101) or without (n=51) passage through the aortic valve. Patients underwent cranial MRI and neurological assessment within 48 h before and after the procedure to assess cerebral embolism. Controls were 32 patients without valvular aortic stenosis who underwent coronary angiography and laevocardiography. FINDINGS 22 of 101 patients (22%) who underwent retrograde catheterisation of the aortic valve had focal diffusion-imaging abnormalities in a pattern consistent with acute cerebral embolic events after the procedure; three of these patients (3%) had clinically apparent neurological deficits. By contrast, none of the patients without passage of the valve, or any of the controls, had evidence of cerebral embolism as assessed by MRI. INTERPRETATION Patients with valvular aortic stenosis who undergo retrograde catheterisation of the aortic valve have a substantial risk of clinically apparent cerebral embolism, and frequently have silent ischaemic brain lesions. Patients should be informed about these risks, and this procedure should be used only in patients with unclear echocardiographical findings when additional information is necessary for clinical management.

Proton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with AD

Background: The reduction of N-acetylaspartate (NAA) detected by proton MR spectroscopy (1H-MRS) represents a robust but unspecific marker for neuronal loss or dysfunction. Objective: To apply 1H-MRS in two brain regions that reflect the characteristic spatial distribution of neuronal loss in AD. These regions are the medial temporal lobe (MTL), which is affected early in AD, and the primary motor and sensory cortex (central region), which is affected late in the disease and might serve as an intraindividual control region in mild to moderate disease stages. Methods: Twenty patients and 18 volunteers underwent 1H-MRS in both brain areas. The metabolic ratios of NAA/creatine and choline/creatine were determined. Additionally, the metabolic ratios of the MTL were divided by the ratios of the central region to assess the relative change in the MTL in individual subjects. All ratios were correlated with psychometric test scores. Results: A significant reduction of NAA/creatine and choline/creatine ratios was detected in the MTL of patients with AD. In the central region, no significant difference between the groups was found. NAA/creatine (MTL/central region) was reduced in patients with AD and showed a correlation with the Mini-Mental State Examination and the cognitive part of the Alzheimer Disease Assessment Scale scores. Choline/creatine (MTL/central region) did not show a significant difference between groups. Conclusion: Assessing the distribution of NAA/creatine reduction guided by the expected neuropathologic change can improve the role of 1H-MRS in the assessment of AD. The disease severity can be monitored by relative reduction of NAA/creatine in the MTL in comparison with an intraindividual unaffected control region.

Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in Deep Cerebral Venous Thrombosis

BACKGROUND Diffusion-weighted (DWI) and perfusion-weighted (PI) MRI are highly sensitive techniques for early diagnosis of arterial infarction, but little data on venous cerebral ischemia are available. We describe a case in which DWI, PI, and fast T2-weighted sequences were performed in the acute phase of deep cerebral venous thrombosis (CVT). CASE DESCRIPTION An 11-year-old girl with Crohns disease developed deep CVT in which extensive edema was shown in the deep gray matter on T2-weighted sequence images. Isotropic echo-planar DWI demonstrated a local augmentation of the apparent diffusion coefficient (1.1 to 1.6x10(-3) mm2/s), consistent with vasogenic edema. In dynamic contrast-enhanced PI, the regional cerebral blood volume was increased and the passage time of the contrast bolus was markedly prolonged. Clinically, the patient recovered totally after intravenous full-dose heparinization. T2 abnormalities, apparent diffusion coefficient values (0.8 to 0.92x10(-3) mm2/s), and brain perfusion alterations resolved without damage to brain tissue. CONCLUSIONS Unlike arterial infarction, DWI demonstrated vasogenic edema in a patient with deep CVT, which proved to be reversible in follow-up magnetic resonance imaging. PI showed areas with extensive venous congestion, but perfusion deficits were missing. Therefore, we believe that DWI and PI may play a role in detecting venous congestion in CVT and in prospective differentiation of vasogenic edema and venous infarction.

MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Abstract Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease is an intrinsic motor neuron disease.

Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients.

In this 1H-MRS follow-up study of the medial temporal lobe (MTL) in patients with AD, the authors report a correlation of N-acetylaspartate (NAA)/creatine (Cr) with cognitive decline. Severely progressed patients showed a reduction, whereas stable or mildly progressed subjects showed a slight increase of NAA/Cr. The reduction of NAA/Cr in the MTL represents a correlate of cognitive deterioration in AD, whereas it is of limited use to detect subtle changes over time in clinically stable patients.

In-vivo proton MR-spectroscopy of the human brain: Assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration

Summary. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method to investigate changes in brain metabolite composition in different cerebral diseases.We performed proton spectroscopy in patients with dementia of the Alzheimers type (AD) and in patients with motor neuron disease (MND) with the aim to detect the specific metabolic pattern for these neurodegenerative disorders.In the MND group we found a significant reduction of NAA/tCr metabolite ratios in the motor cortex, which correlates with the disease severity and the clinical lateralization of neurological symptoms and further decreases in the time course of the disease. In AD patients a reduction of NAA/tCr was observed in the medial temporal lobe.Since NAA is exclusively expressed in neurons as shown by immunohistochemical studies, reduced NAA levels suggest neuronal loss or dysfunction in the observed regions.The observed regional metabolic alterations reflect the neuronal basis of the characteristic neurological symptoms in AD (dementia) and MND (muscular palsy) and mirrors the disease progress over time.

Performance of ACR Lung-RADS in a Clinical CT Lung Screening Program

PURPOSE The aim of this study was to assess the effect of applying ACR Lung-RADS in a clinical CT lung screening program on the frequency of positive and false-negative findings. METHODS Consecutive, clinical CT lung screening examinations performed from January 2012 through May 2014 were retroactively reclassified using the new ACR Lung-RADS structured reporting system. All examinations had initially been interpreted by radiologists credentialed in structured CT lung screening reporting following the National Comprehensive Cancer Networks Clinical Practice Guidelines in Oncology: Lung Cancer Screening (version 1.2012), which incorporated positive thresholds modeled after those in the National Lung Screening Trial. The positive rate, number of false-negative findings, and positive predictive value were recalculated using the ACR Lung-RADS-specific positive solid/part-solid nodule diameter threshold of 6 mm and nonsolid (ground-glass) threshold of 2 cm. False negatives were defined as cases reclassified as benign under ACR Lung-RADS that were diagnosed with malignancies within 12 months of the baseline examination. RESULTS A total of 2,180 high-risk patients underwent baseline CT lung screening during the study interval; no clinical follow-up was available in 577 patients (26%). ACR Lung-RADS reduced the overall positive rate from 27.6% to 10.6%. No false negatives were present in the 152 patients with >12-month follow-up reclassified as benign. Applying ACR Lung-RADS increased the positive predictive value for diagnosed malignancy in 1,603 patients with follow-up from 6.9% to 17.3%. CONCLUSIONS The application of ACR Lung-RADS increased the positive predictive value in our CT lung screening cohort by a factor of 2.5, to 17.3%, without increasing the number of examinations with false-negative results.

Diffusion Tensor Pyramidal Tractography in Patients With Anterior Choroidal Artery Infarcts

BACKGROUND AND PURPOSE: Anterior choroidal artery (AchoA) stroke often evolves into undulating hemipareses, which sometimes progress to high-grade hemiparesis or hemiplegia but may also completely regress. Spatial relationships of AchoA infarcts to corticospinal tracts (CSTs) and CST integrity were investigated with diffusion tensor imaging (DTI) to identify prognostic parameters related to diffusion anisotropy changes in AchoA stroke. MATERIALS AND METHODS: Twenty-five AchoA stroke patients were prospectively examined with 3T DTI and diffusion tensor tractography (DTT) within a 3-day mean interval after onset. Analysis included the following: 1) stroke size on diffusion-weighted imaging; 2) fractional anisotropy (FA) and apparent diffusion coefficients at the largest stroke extents versus contralateral homologous structures; 3) lesion location related to CST (“involvement”); 4) amount of fiber trajectories of affected versus nonaffected CST (“fiber ratio”); and 5) presence of ipsilateral fiber disruption. Imaging findings were related to clinical status 3 months after symptom onset with respect to favorable, moderate, or unfavorable motor outcome. RESULTS: FA differences (due to FA reduction in the affected versus nonaffected hemisphere) were significantly higher for patients with unfavorable outcome (P=.03). Patients with favorable outcome had nearly symmetrical FA. CSTs were involved in ischemic lesions in all but 2 patients (complete involvement, n=3; partial, n=20). Two CSTs were completely disrupted, and both patients were hemiplegic (no disruption, n=14; partial disruption, n=9). Fiber disruption and CST involvement correlated negatively with motor score after AchoA stroke (P < .01), whereas infarct size did not. CONCLUSION: DTT may explain resulting motor dysfunction in patients with AchoA infarcts with more notably decreased FA being an indicator for unfavorable outcome.

Reversible changes in echo planar perfusion- and diffusion-weighted MRI in status epilepticus

Abstract Perfusion imaging (PI) demonstrated increased perfusion and diffusion-weighted imaging (DWI) showed high signal limited to the left temporoparietal cortex in a 68-year-old man with nonconvulsive status epilepticus. The EEG showed a slow delta-wave focus. The patient recovered and PI, DWI and EEG changes completely resolved.