Friedhelm E. Zanella

Clinical application of proton magnetic resonance spectroscopy in the diagnosis of intracranial mass lesions

Diagnosis of primary and secondary brain tumours and other focal intracranial mass lesions based on imaging procedures alone is still a challenging problem. Proton magnetic resonance spectroscopy (1H-MRS) gives completely different information related to cell membrane proliferation, neuronal damage, energy metabolism and necrotic transformation of brain or tumour tissues. Our purpose was to evaluate the clinical utility of 1H-MRS added to MRI for the differentiation of intracranial neoplastic and non-neoplastic mass lesions. 176 mostly histologically verified lesions were studied with a constant clinically available single volume 1H-MRS protocol following routine MRI. 12 spectra (6.8%) were not of satisfactory diagnostic quality; 164 spectroscopic data sets were therefore available for definitive evaluation. Our study shows that spectroscopy added to MRI helps in tissue characterization of intracranial mass lesions, thereby leading to an improved diagnosis of focal brain disease. Non-neoplastic lesions such as cerebral infarctions and brain abscesses are marked by decreases in choline (Cho), creatine (Cr) and N-acetyl-aspartate (NAA), while tumours generally have elevated Cho and decreased levels of Cr and NAA. Gliomas exhibit significantly increased Cho and lipid formation with higher WHO tumour grading. Metastases have elevated Cho similar to anaplastic astrocytomas, but can be differentiated from high-grade gliomas by their higher lipid levels. Extra-axial tumours, i.e. meningiomas and neurinomas, are characterized by a nearly complete absence of the neuronal marker NAA. The additive information of 1H-MRS led to a 15.4%-higher number of correct diagnoses, to 6.2% fewer incorrect and 16% fewer equivocal diagnoses than with structural MRI data alone.

Cerebral Gliomas: Diffusional Kurtosis Imaging Analysis of Microstructural Differences

PURPOSE To characterize the non-Gaussian diffusion patterns of cerebral glioma microstructure with respect to the different glioma grades by using a new method called diffusional kurtosis (DK) imaging. MATERIALS AND METHODS In this study with institutional review board approval and patient consent, diffusional measures of mean kurtosis (MK), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were compared prospectively. Data were normalized to the contralateral white matter. A Mann-Whitney test was used to compare each histologic glioma subtype regarding the diffusion measurements. Receiver operating characteristic curves were used to test for the parameter with the best sensitivity and specificity for glioma grade discrimination. RESULTS In 34 patients with cerebral gliomas (five World Health Organization [WHO] grade II astrocytomas, 13 WHO grade III astrocytomas, and 16 WHO grade IV glioblastomas multiforme), significantly different diffusion patterns were found among the three glioma groups. MK values increased with higher glioma malignancy, whereas ADCs tended to decrease with higher malignancy; FA values did not differ significantly among tumor groups. Significant differences between astrocytoma grades WHO II and WHO III were demonstrated only by DK values. Area under the receiver operating characteristic curve was highest for normalized MK (0.972) during testing to discriminate between low- and high-grade gliomas. CONCLUSION This study demonstrates specific diffusion patterns for low- and high-grade gliomas, showing that DK imaging is able to depict microstructural changes within glioma tissue and is able to help differentiate among glioma grades. (c) RSNA, 2010.

Tracking the Mind's Image in the Brain I: Time-Resolved fMRI during Visuospatial Mental Imagery

Mental imagery, the generation and manipulation of mental representations in the absence of sensory stimulation, is a core element of numerous cognitive processes. We investigate the cortical mechanisms underlying imagery and spatial analysis in the visual domain using event-related functional magnetic resonance imaging during the mental clock task. The time-resolved analysis of cortical activation from auditory perception to motor response reveals a sequential activation of the left and right posterior parietal cortex, suggesting that these regions perform distinct functions in this imagery task. This is confirmed by a trial-by-trial analysis of correlations between reaction time and onset, width, and amplitude of the hemodynamic response. These findings pose neurophysiological constraints on cognitive models of mental imagery.

Functional imaging of visuospatial processing in Alzheimer's disease

Alzheimers disease (AD) is known to cause a variety of disturbances of higher visual functions that are closely related to the neuropathological changes. Visual association areas are more affected than primary visual cortex. Additionally, there is evidence from neuropsychological and imaging studies during rest or passive visual stimulation that the occipitotemporal pathway is less affected than the parietal pathway. Our goal was to investigate functional activation patterns during active visuospatial processing in AD patients and the impact of local cerebral atrophy on the strength of functional activation. Fourteen AD patients and fourteen age-matched controls were measured with functional magnetic resonance imaging (fMRI) while they performed an angle discrimination task. Both groups revealed overlapping networks engaged in angle discrimination including the superior parietal lobule (SPL), frontal and occipitotemporal (OTC) cortical regions, primary visual cortex, basal ganglia, and thalamus. The most pronounced differences between the two groups were found in the SPL (more activity in controls) and OTC (more activity in patients). The differences in functional activation between the AD patients and controls were partly explained by the differences in individual SPL atrophy. These results indicate that parietal dysfunction in mild to moderate AD is compensated by recruitment of the ventral visual pathway. We furthermore suggest that local cerebral atrophy should be considered as a covariate in functional imaging studies of neurodegenerative disorders.

Impairment of Cerebral Perfusion and Infarct Patterns Attributable to Vasospasm After Aneurysmal Subarachnoid Hemorrhage A Prospective MRI and DSA Study

Background and Purpose— The objective of this study was to investigate disturbance of perfusion and infarct patterns attributable to cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Methods— One hundred seventeen patients with aneurysmal SAH specifically selected at high risk for CVS were enrolled in this prospective study. One hundred twelve patients underwent surgical (n=63) or endovascular (n=59) therapy. For assessment of CVS, relative diameter changes of proximal and distal vessel segments on follow-up angiography at day 7±3 after SAH were analyzed in relation to baseline measurements, and cerebral circulation times were measured. Postprocedure MRI was undertaken selectively at four time points: within 3 days, between days 4 and 6, day 7 to 14, and day 15 to 28 from onset of SAH, including perfusion- and diffusion-weighted images. Procedure-related lesions were excluded and CVS-associated infarct patterns analyzed. Results— Occurrence of angiographic CVS was as high as 87.5% between days 7 and 14 and 52.5% showed new infarcts. Eighty-one percent of the infarcts were related to severe CVS (vascular narrowing >66%) and significant (P<0.001) cerebral circulation times prolongation of 8.47±2.25 seconds (time-to-peak delay on perfusion-weighted image: 6.52±4.75 seconds), 16% were associated with moderate CVS (34% to 66% vascular narrowing; cerebral circulation times prolongation: 4.72±0.66 seconds). Besides territorial (47%), lacunar (20%), and watershed infarcts (26%), in 7%, band-like cortical lesions developed without evidence for severe CVS. Conclusions— CVS after SAH may involve the complete arterial system from the circle of Willis up to the distal vessel segments. Depending on the variable types of collateral flow, location of affected vessels segments as well as the degree of CVS may induce different infarct patterns.

Phosphorus and proton magnetic resonance spectroscopy demonstrates mitochondrial dysfunction in early and advanced Parkinson's disease

Mitochondrial dysfunction hypothetically contributes to neuronal degeneration in patients with Parkinsons disease. While several in vitro data exist, the measurement of cerebral mitochondrial dysfunction in living patients with Parkinsons disease is challenging. Anatomical magnetic resonance imaging combined with phosphorus and proton magnetic resonance spectroscopic imaging provides information about the functional integrity of mitochondria in specific brain areas. We measured partial volume corrected concentrations of low-energy metabolites and high-energy phosphates with sufficient resolution to focus on pathology related target areas in Parkinsons disease. Combined phosphorus and proton magnetic resonance spectroscopic imaging in the mesostriatal region was performed in 16 early and 13 advanced patients with Parkinsons disease and compared to 19 age-matched controls at 3 Tesla. In the putamen and midbrain of both Parkinsons disease groups, we found a bilateral reduction of high-energy phosphates such as adenosine triphophosphate and phosphocreatine as final acceptors of energy from mitochondrial oxidative phosphorylation. In contrast, low-energy metabolites such as adenosine diphophosphate and inorganic phosphate were within normal ranges. These results provide strong in vivo evidence that mitochondrial dysfunction of mesostriatal neurons is a central and persistent phenomenon in the pathogenesis cascade of Parkinsons disease which occurs early in the course of the disease.

Quality control after cochlear implant surgery by means of rotational tomography.

Objective: To investigate the intracochlear electrode position in using rotational tomography in adult cochlear implant patients. Study Design: Retrospective. Setting: Tertiary referral center. Patients: Eighteen adult patients being implanted either with a Nucleus straight electrode array or a Contour electrode with a total of 22 implanted ears. Preoperative computed tomography had been without evidence for obliteration, ossification, or malformation of the cochlea. Intervention: Rotational tomography. Main Outcome Measures: The intracochlear electrode position was evaluated with regard to scala tympani, scala vestibuli, and a dislocation from one scala to the other. The intraoperative procedure was compared with the electrode position by analyzing the operating reports. Results: Preliminary results indicate, respectively, that there is a higher incidence of intracochlear trauma in using the Contour electrode array than expected with a more frequent dislocation of electrode arrays from scala tympani to scala vestibuli and that there is a higher rate of scala vestibuli insertions. Conclusions: The impact of these findings may influence further developments of electrode arrays as well as surgical techniques for implantation.

Functional MRI using sensitivity-encoded echo planar imaging (SENSE-EPI)

Parallel imaging methods become increasingly available on clinical MR scanners. To investigate the potential of sensitivity-encoded single-shot EPI (SENSE-EPI) for functional MRI, five imaging protocols at different SENSE reduction factors (R) and matrix sizes were compared with respect to their noise characteristics and their sensitivity toward functional activation in a motor task examination. At constant echo times, SENSE-EPI was either used to shorten the single volume acquisition times (TR(min)) at matrix size 128 x 100 (22 slices) from 3.9 s (no SENSE) to 2.0 s at R = 3, or to increase the matrix size to 192 x 153 (22 slices), resulting in TR(min) = 5.3 s for R = 2 or TR(min) = 3.4 s for R = 3. At the lower resolution, the bisection of echo train length (R = 2) substantially reduced distortions and blurring, while signal-to-noise and statistical power (measured by cluster size and maximum t value per unit time) were hardly reduced. At R = 3 the additional gain in speed and distortion reduction was quite small, while signal-to-noise and statistical power dropped significantly. With enhanced spatial resolution the time course signal-to-noise was better than expected from theory for purely thermal noise because of a reduced contribution of physiological noise, and statistical power almost reached that of the regular, low-resolution single-shot EPI, with a slight drop off toward R = 3. Thus, SENSE-EPI allows to substantially increase speed and spatial resolution in fMRI. At SENSE reduction factors up to R = 2, the potential drawbacks regarding signal-to-noise and statistical power are almost negligible.

Activity patterns in human motion-sensitive areas depend on the interpretation of global motion

Numerous imaging studies have contributed to the localization of motion-sensitive areas in the human brain. It is, however, still unclear how these areas contribute to global motion perception. Here, we investigate with functional MRI whether the motion-sensitive area hMT+/V5 is involved in perceptual segmentation and integration of motion signals. Stimuli were overlapping moving gratings that can be perceived either as two independently moving, transparent surfaces or as a single surface moving in an intermediate direction. We examined whether motion-sensitive area hMT+/V5 is involved in mediating the switches between the two percepts. The data show differential activation of hMT+/V5 with perceptual switches, suggesting that these are associated with a reconfiguration of cell assemblies in this area.

Diffusion tensor imaging in patients with adult chronic idiopathic hydrocephalus.

OBJECTIVEDiffusion tensor imaging (DTI) parameters were investigated in patients with chronic idiopathic hydrocephalus to evaluate microstructural changes of brain tissue caused by chronic ventricular dilatation. METHODSEleven patients fulfilling the criteria for possible or probable idiopathic normal pressure hydrocephalus and 10 healthy control subjects underwent MRI at 3 Tesla, including DTI with 12 gradient directions. Patients were scanned before lumbar cerebrospinal fluid (CSF) withdrawal tests. Differences in fractional anisotropy (FA) and mean diffusivity (MD) between patients and controls were assessed using 2 different methods: manual definition of regions of interest and a fully automated method, TBSS (Tract-Based Spatial Statistics). DTI parameters were correlated with clinical findings. RESULTSCompared with the control group, patients with chronic idiopathic hydrocephalus had significantly higher MD values in both the periventricular corticospinal tract (CST) and the corpus callosum (CC), whereas FA values were significantly higher in the CST but lower in the CC. DTI parameters of the CST correlated with the severity of gait disturbances. CONCLUSIONMicrostructural changes in periventricular functionally relevant white matter structures (CSF, CC) in chronic idiopathic hydrocephalus can be visualized using DTI. Further studies should investigate the change of DTI parameters after CSF shunting and its relation to neurologic outcome.