Helmut Rumpel

Case-control study of diffusion tensor imaging in Parkinson’s disease

Background: Preliminary work has shown that diffusion tensor MRI (DTI) may contribute to the diagnosis of Parkinson’s disease (PD). Objectives: We conducted a large, prospective, case control study to determine: (1) if fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in the basal ganglia and substantia nigra are different between patients with PD and healthy controls; and (2) the predictive value of these parameters and their clinical utility. Methods: DTI imaging was carried out in patients with PD and controls. FA and ADC values were obtained from various brain structures on the DTI scan using the diffusion tensor taskcard. The structures studied were: caudate, putamen, globus pallidus, thalamus and substantia nigra. Results: 151 subjects (73 PD patients, 41 men, 32 women; mean age 63.6 years) and 78 age and sex matched control subjects were studied. The FA value of the substantia nigra in patients with PD was lower compared with controls (0.403 vs 0.415; p = 0.001). However, no significant differences were demonstrated for FA or ADC values of other structures. Multiple regression analysis revealed that the clinical severity of PD correlated inversely with the FA value in the substantia nigra in patients with PD (regression coefficient −0.019). No single FA value had both a high positive and negative predictive power for PD. Conclusions: We demonstrated in a large, prospective, case control study that the FA value in the substantia nigra on DTI was lower in PD compared with healthy controls, and correlated inversely with the clinical severity of PD. Further longitudinal studies would be helpful to assess the clinical utility of serial FA measurements of the substantia nigra in objective quantification of disease progression and monitoring of the therapeutic response.

Hepatic Metastases: In Vivo Assessment of Perfusion Parameters at Dynamic Contrast-enhanced MR Imaging with Dual-Input Two-Compartment Tracer Kinetics Model

This study was institutional review board approved, with waived patient consent for retrospective analysis of the data. The hepatic perfusion at dynamic contrast material-enhanced magnetic resonance (MR) imaging was commonly described and assessed by using a dual-input one-compartment tracer kinetics model. Although the tracer kinetics in normal liver parenchyma can be described by using a single compartment, functional changes in the tumor microenvironment can result in distinctly different tracer behavior that entails a second tissue compartment. A dual-input two-compartment model is proposed to describe the tracer behavior in hepatic metastases. The authors applied this model to the dynamic MR imaging data obtained in three patients. Perfusion parameter maps and region-of-interest analysis revealed that tracer behavior in hepatic metastases-in contrast to that in surrounding normal liver tissue, which effectively involves one compartment-can be described by using two compartments.

Temporal lobe changes following radiation therapy: imaging and proton MR spectroscopic findings

Abstract Radiation therapy for nasopharyngeal carcinoma affects the temporal lobes. This paper characterizes proton MR spectroscopic findings of the temporal lobes and correlates them with imaging changes. Single-voxel proton MR spectroscopic examinations were acquired from 13 healthy adult volunteers (25 spectra) and 18 patients (28 spectra). All patients had biopsy-confirmed nasopharyngeal carcinoma and were previously treated with radiation therapy. Six patients (33 %) had a single treatment and12 (67 %) patients had two treatments. Point resolved spectroscopy (PRESS) method was used (TR = 3000 ms, TE = 135 ms) and data processed automatically using the LCModel software package for metabolite quantification. Voxel size and geometry were adapted to the lesion to reduce skull-base lipid contamination. The metabolites were quantitated relative to water signal. For each location, an additional non-water-suppressed reference scan in fully relaxed conditions was performed. The imaging findings were divided into four categories: I, normal; II, edema only; III, contrast-enhancing lesions; and IV, cystic encephalomalacia. The N-acetyl-aspartate levels were reduced in 27 (96 %) spectra. Choline was increased in 3 (11 %), normal in 4 (14 %), and reduced in 21 (75 %) spectra. The creatine level was normal in 8 (29 %) spectra and reduced in 20 (71 %) spectra. Imaging showed 4 (14 %) spectra with category-I imaging findings; 5 (18 %) spectra with category-II findings; 15 (54 %) spectra with category-III findings; and 4 (14 %) spectra with category-IV findings. Magnetic resonance spectroscopy showed reduced N-acetyl-aspartate in radiation-induced temporal lobe changes. Creatine levels were relatively more stable. Choline levels may be increased, normal, or reduced. Imaging findings ranged from normal to contrast-enhancing lesions and cystic encephalomalacia.

Temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma: 1H MR spectroscopic findings.

PURPOSE To observe the patterns of radiation-induced temporal lobe necrosis (TLN) following radiation therapy for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS Twenty-five proton magnetic resonance spectroscopic (1H MRS) examinations were acquired from 13 healthy adult volunteers for comparison with data from the patient population. There were 18 patients (28 spectra) with radiologic evidence of TLN and all patients were confirmed cases of NPC treated with radiation therapy. Six patients (33%) had a single treatment while 12 (67%) patients had two treatments. All 1H MRS examinations were performed on a 2-T whole body system (Bruker) using the point-resolved spectroscopy (PRESS) method with TE = 135 ms, TR = 3000 ms, and data processed automatically using the LCModel software package for metabolite quantification. RESULTS The N-acetyl-aspartate (NAA) levels were reduced in all except one spectrum (96%). Choline (Cho) was increased in 3 (11%), normal in 4 (14%), and reduced in 21 (75%) spectra. The creatine (Cr) level was normal in 8 (29%) spectra and reduced in 20 (71%) spectra. In four patients with normal imaging findings 1H MRS was abnormal. CONCLUSION 1H MRS can characterize radiation-induced TLN. Spectra with increased Cho can be mistaken for neoplasm. Spectroscopy can also identify metabolic derangement before imaging.

High plasma cyst(e)ine level may indicate poor clinical outcome in patients with acute stroke: possible involvement of hydrogen sulfide.

Abstract Cysteine is known to cause neuronal cell death and has been reported to be elevated in brain ischemia, but it has not been studied in clinical stroke. In this study, we correlated plasma levels of cyst(e)ine with long-term clinical outcome at 3 months in acute stroke. Patients were classified into 3 groups at 3 months as follows: good outcome (Rankin 0-1, n = 11), poor outcome (Rankin 2-5, n = 20), and dead (n = 5). Their plasma cyst(e)ine levels within 24 hours of stroke onset were 61 ± 12, 67 ± 9, and 82 ± 14 μmol/L (standard deviation), respectively. The correlation between early plasma cyst(e)ine levels and long-term clinical outcome assessed at 3 months is significant with p < 0.001. None of the other 4 amino acids studied showed any significant correlation. Cyst(e)ine was also significantly elevated in patients who had early stroke deterioration (p < 0.02). Dose-dependent administration of cysteine increased the infarct volume by approximately 30% in a rat stroke model. This effect of cysteine was abolished by aminooxyacetic acid, an inhibitor of the enzyme cystathionine β-synthase that converts cysteine to hydrogen sulfide (H2S), indicating that this novel neuromodulator may be acting as a mediator of ischemic brain damage. Raised plasma cyst(e)ine in patients with stroke may reflect increased production of H2S in the brain and thus predispose to poor outcome in clinical stroke. Inhibition of H2S formation may therefore be a novel approach in acute stroke therapy.

Finite Element Analysis Predicts Large Optic Nerve Head Strains During Horizontal Eye Movements.

PURPOSE We combined finite element (FE) analysis and dynamic magnetic resonance imaging (MRI) to estimate optic nerve head (ONH) strains during horizontal eye movements, and identified factors influencing such strains. We also compared ONH strains (prelamina, lamina cribrosa, and retrolamina strains) induced by eye movements to those induced by IOP. METHODS The ocular globes and orbits of a healthy subject were visualized during horizontal eye movements (up to 13°), using dynamic MRI. A baseline FE model of one eye was reconstructed in the primary gaze position, including details from the orbital and ONH tissues. Finite element-derived ONH strains induced by eye movements were compared to those resulting from an IOP of 50 mm Hg. Finally, a FE sensitivity study was performed, in which we varied the stiffness of all ONH connective tissues, to understand their influence on ONH strains. RESULTS Our models predicted that, during horizontal eye movements, the optic nerve pulled the ONH posteriorly. Optic nerve head strains following a lateral eye movement of 13° were large and higher than those resulting from an IOP of 50 mm Hg. These results held true even with variations in connective tissue stiffness. We also found that stiff sclerae reduced lamina cribrosa and prelamina strains during eye movements, but stiff optic nerve sheaths significantly increased those strains. CONCLUSIONS Our models predicted high ONH strains during eye movements, which were aggravated with stiffer optic nerve sheaths. Further studies are needed to explore links between ONH strains induced by eye movements and axonal loss in glaucoma.

Is myo-inositol a measure of glial swelling after stroke? A magnetic resonance study.

To determine whether the hypothesis that the phenomenon of persistent cytotoxic edema in the subacute stage of ischemic stroke is in fact associated with the glial population. This is done by assessing the evolution of both the apparent diffusion coefficient (ADC) and the glial‐specific marker myo‐inositol (Ins) in a group of patients, and by comparing the results with the total cellular density by means of the creatine (Cre) level.

Transcallosal diffusion tensor abnormalities in predominant gait disorder parkinsonism

BACKGROUND There have been no previous diffusion tensor imaging (DTI) studies comparing Parkinsons disease (PD) with postural instability and gait disorder (PIGD) parkinsonism. OBJECTIVE Utilizing DTI with 2-region tractography, we conducted a case control study to determine if different brain regions representing the neural network of the motor system are differentially affected in PIGD compared to PD and controls. METHODS On a 3 T MR machine, using manual ROI (regions of interest) we determined the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in anatomical brain regions representing the extrapyramidal, pyramidal, and transcallosal tracts, aided by 2-region tractography. FA and ADC were correlated with the Tinetti score (measure of gait and balance). RESULTS Sixty-five subjects (21 PD, 25 PIGD, 19 controls) were included in the analysis. We demonstrated greater ADC abnormalities in the extrapyramidal, pyramidal and transcallosal motor systems in PIGD compared to controls. Multivariate analysis taking into consideration various clinical variables showed that the FA (p = 0.02) and ADC (p = 0.001) values in the corpus callosum body differentiated PIGD from PD. PIGD with low Tinetti score had a lower FA (p = 0.02) and a higher ADC value (corpus callosum body) (p = 0.03) compared to those with a high score. CONCLUSIONS We demonstrated for the first time that DTI abnormalities along the transcallosal motor tract in the body of the corpus callosum, but not the substantia nigra, differentiated PIGD from PD, and the degree of corpus callosum body abnormality correlated with the Tinetti score (a measure of risk of falls).

Neurological changes following radiation therapy for head and neck tumours

Radiation therapy is widely used in the treatment of head and neck tumours either as a primary form of treatment or a supplementary modality. Although the benefits of radiation therapy are well established, this treatment modality is not without untoward consequences and complications. The intent of this paper is to highlight the neurological complications that may follow the treatment for head and neck malignancies, in particular, following radiation therapy for nasopharyngeal carcinoma.

Intravoxel incoherent imaging of renal fibrosis induced in a murine model of unilateral ureteral obstruction

PURPOSE To evaluate non-invasive imaging biomarkers for assessing renal fibrosis. DWI is used to assess renal function; intravoxel incoherent motion (IVIM) provides additional measures of perfusion-related diffusion (D*, blood flow; f, perfusion fraction). We aim to determine if reduced ADC seen in renal fibrosis is attributable to perfusion-related diffusion changes or to known reduction in tissue diffusivity (D). MATERIALS AND METHODS Unilateral ureteral obstruction (UUO) was created in six mice to induce renal fibrosis. DWI was performed the day before and 7 days post-UUO. A range of b-values from 0 to 1200 s/mm(2) were used. IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of both kidneys was performed in all mice. Results were analyzed using the paired t-test with P<0.05 considered statistically significant. RESULTS D and f were significantly lower in the ligated kidneys at Day 7 compared to before ligation and no significant difference was found for D*. Comparing non-ligated and ligated kidneys within the same mouse at Day 7, significantly lower D values were observed in the ligated kidneys, while no significant difference was found for f and D*, although the values of f were generally lower. Histopathological analysis confirmed development of fibrosis and reduction in glomeruli in all the ligated kidneys at Day 7. CONCLUSION Our study shows that the reduction in ADC seen in renal fibrosis is attributable not only to reduced D as previously encountered but also a decrease in vascularity as assessed by f. Reduction in f is possibly related to a reduction in glomeruli.