Hans-Jörg Wittsack

Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging

The utility of perfusion-weighted magnetic resonance imaging (PW-MRI) for detecting changes in regional cerebral blood flow (rCBF) in patients with mild cognitive impairment (MCI) and early Alzheimers disease (AD) was evaluated. Thirteen cognitively normal (CN) elderly subjects, 35 mostly amnestic MCI subjects and 20 subjects with mild probable AD were enrolled. During i.v. injection of gadopentetate dimeglumine, a dynamic T2*-weighted single-shot EPI sequence was conducted using a 1.5-T scanner. Frontobasal (FROB), temporoparietal (TPAR), mesiotemporal (MTMP), anterior and posterior cingular (ACING, PCING), amygdala (AMYG), thalamus and cerebellar brain regions were studied. rCBF was computed from regional cerebral blood volume and arterial input function and normalised to white matter. Images were analysed by manually placed regions of interest using anatomical coregistration. Significant decreases of rCBF were detected in MCI vs. CN in MTMP (-23%), AMYG (-20%) and ACING (-15%) with no further decline in mild AD. In PCING hypoperfusion (-10%) was confined to AD. These hypoperfusional changes are a possible correlate of localised impairment of CNS function. In FROB no perfusion changes were observed between diagnostic groups, but hyperperfusion was observed in mild dementia stages, possibly reflecting functional compensatory mechanisms. These data suggest that PW-MRI detects specific changes in rCBF not only in AD, but also in amnestic MCI, a disorder suggested to largely represent a pre-dementia stage of AD. This method may thus be useful in both research and clinical applications to detect early functional brain changes in the pathogenesis of dementias.

Kidney Transplant: Functional Assessment with Diffusion-Tensor MR Imaging at 3T

PURPOSE To evaluate the feasibility of diffusion-tensor (DT) imaging at 3 T for functional assessment of transplanted kidneys. MATERIALS AND METHODS This study was approved by the local ethics committee; written informed consent was obtained. Between August 2009 and October 2010, 40 renal transplant recipients were prospectively included in this study and examined with a clinical 3-T magnetic resonance (MR) imager. An echo-planar DT imaging sequence was performed in coronal orientation by using five b values (0, 200, 400, 600, 800 sec/mm(2)) and 20 diffusion directions. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were determined for the cortex and medulla of the transplanted kidney. Relationships between FA, ADC, and allograft function, determined by the estimated glomerular filtration rate (eGFR), were assessed by using Pearson correlation coefficient. ADC and FA were compared between patients with good or moderate allograft function (group A; eGFR > 30 mL/min/1.73 m(2)) and patients with impaired function (group B; eGFR ≤ 30 mL/min/1.73 m(2)) by using a student t test. P < .05 indicated a statistically significant difference. RESULTS Mean FA of the renal medulla and cortex was significantly higher in group A (0.39 ± 0.06 and 0.17 ± 0.4) compared with group B (0.27 ± 0.05 and 0.14 ± 0.03) (P < .001 and P = .009, respectively). Mean ADCs of renal cortex and medulla were significantly higher in group A than in group B (P = .007 and P = .01, respectively). In group B, mean medullary FA was significantly lower in patients whose renal function did not recover (0.22 ± 0.02) compared with those with stable allograft function at 6 months (0.29 ± 0.05, P < .001). There was significant correlation between eGFR and medullary FA (r = 0.65, P < .001), cortical ADC (r = 0.43, P = .003), and medullary ADC (r = 0.35, P = .01). CONCLUSION DT imaging is a promising noninvasive technique for functional assessment of renal allografts. FA values in the renal medulla exhibit a good correlation with renal function.

Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimers disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

Comparison of different mathematical models of diffusion-weighted prostate MR imaging

PURPOSE To evaluate which mathematical model (monoexponential, biexponential, statistical, kurtosis) fits best to the diffusion-weighted signal in prostate magnetic resonance imaging (MRI). MATERIALS AND METHODS 24 prostate 3-T MRI examinations of young volunteers (YV, n=8), patients with biopsy proven prostate cancer (PC, n=8) and an aged matched control group (AC, n=8) were included. Diffusion-weighted imaging was performed using 11 b-values ranging from 0 to 800 s/mm(2). RESULTS Monoexponential apparent diffusion coefficient (ADC) values were significantly (P<.001) lower in the peripheral (PZ) zone (1.18±0.16 mm(2)/s) and the central (CZ) zone (0.73±0.13 mm(2)/s) of YV compared to AC (PZ 1.92±0.17 mm(2)/s; CZ 1.35±0.21 mm(2)/s). In PC ADC(mono) values (0.61±0.06 mm(2)/s) were significantly (P<.001) lower than in the peripheral of central zone of AC. Using the statistical analysis (Akaike information criteria) in YV most pixels were best described by the biexponential model (82%), the statistical model, respectively kurtosis (93%) each compared to the monoexponential model. In PC the majority of pixels was best described by the monoexponential model (57%) compared to the biexponential model. CONCLUSION Although a more complex model might provide a better fitting when multiple b-values are used, the monoexponential analyses for ADC calculation in prostate MRI is sufficient to discriminate prostate cancer from normal tissue using b-values ranging from 0 to 800 s/mm(2).

Functional evaluation of transplanted kidneys using arterial spin labeling MRI

To investigate non–contrast‐enhanced arterial spin labeling (ASL) MRI for functional assessment of transplanted kidneys at 1.5 Tesla (T) and 3T.

Temporally resolved electrocardiogram-triggered diffusion-weighted imaging of the human kidney: correlation between intravoxel incoherent motion parameters and renal blood flow at different time points of the cardiac cycle.

Purpose:To evaluate the influence of pulsatile blood flow on apparent diffusion coefficients (ADC) and the fraction of pseudodiffusion (FP) in the human kidney. Materials and Methods:The kidneys of 6 healthy volunteers were examined by a 3-T magnetic resonance scanner. Electrocardiogram (ECG)-gated and respiratory-triggered diffusion-weighted imaging (DWI) and phase-contrast flow measurements were performed. Flow imaging of renal arteries was carried out to quantify the dependence of renal blood flow on the cardiac cycle. ECG-triggered DWI was acquired in the coronal plane with 16 b values in the range of 0 s/mm2 and 750 s/mm2 at the time of minimum (MIN) (20 milliseconds after R wave) and maximum renal blood flow (MAX) (197 ± 24 milliseconds after R wave). The diffusion coefficients were calculated using the monoexponential approach as well as the biexponential intravoxel incoherent motion model and correlated to phase-contrast flow measurements. Results:Flow imaging showed pulsatile renal blood flow depending on the cardiac cycle. The mean flow velocity at MIN was 45 cm/s as compared with 61 cm/s at MAX. Fp at MIN (0.29) was significantly lower than at MAX (0.40) (P = 0.001). Similarly, ADCmono, derived from the monoexponential model, also showed a significant difference (P < 0.001) between MIN (ADCmono = 2.14 ± 0.08 × 10−3 mm2/s) and MAX (ADCmono = 2.37 ± 0.04 × 10−3 mm2/s). The correlation between renal blood flow and Fp (r = 0.85) as well as ADCmono (r = 0.67) was statistically significant. Conclusion:Temporally resolved ECG-gated DWI enables for the determination of the diffusion coefficients at different time points of the cardiac cycle. ADCmono and FP vary significantly among acquisitions at minimum (diastole) and maximum (systole) renal blood flow. Temporally resolved ECG-gated DWI might therefore serve as a novel technique for the assessment of pulsatility in the human kidney.

Correlation of biexponential diffusion parameters with arterial spin-labeling perfusion MRI: results in transplanted kidneys.

PurposeThe purpose of the present study was to explore the correlation between diffusion parameters assessed by biexponential analysis and the tissue perfusion measured by arterial spin labeling (ASL) imaging in renal allografts. Material and MethodsSeventeen recipients of renal allograft (11 men and 6 women; mean [SD] age, 53.6 [14.1] years) were included in this study. For diffusion-weighted imaging, a paracoronal echo-planar imaging sequence was acquired with 16 b values (range, b = 0−750 s/mm2) and 6 averages at 1.5 T. For the quantitative assessment of transplanted kidney perfusion, a flow-sensitive alternating inversion recovery true fast imaging with steady precession-ASL technique was applied. No respiratory gating was used. For quantitative analysis, region of interest measurements were performed on parameter maps. The Spearman correlation coefficients were calculated to determine the association between mean serum creatinine levels, estimated glomerular filtration rate, the apparent diffusion coefficient (ADC) of pure diffusion, the ADC of pseudodiffusion, the monoexponential ADC, the fraction of pseudodiffusion, and the tissue perfusion ASL values. ResultsIn the renal cortex, the fraction of pseudodiffusion was 17.4% ± 4.0%, the apparent diffusion coefficient of pure diffusion was 160.7 ± 15.0 × 10−5 mm2/s, the monoexponential ADC was 193.2 ± 16.7 × 10−5 mm2/s, and the ADC of pseudodiffusion was 1421.0 ± 237.7 × 10−5 mm2/s. Mean cortical perfusion of renal allografts, as assessed with ASL imaging, was 247.2 ± 75.0 mL/100 g/min. There was a significant correlation between ASL perfusion and the fraction of pseudodiffusion (r = 0.68; P < 0.005) but not with the other diffusion coefficients. Both ASL perfusion and the fraction of pseudodiffusion exhibited a significant correlation with serum creatinine levels (r = 0.51 and r= 0.53, respectively; P < 0.05) and estimated glomerular filtration rate (r = 0.63 and r = 0.54, respectively; P < 0.05). ConclusionsThis is the first study that shows a significant correlation between renal allograft perfusion, as assessed with ASL perfusion measurements, and the fraction of pseudodiffusion derived from biexponential diffusion-weighted imaging measurements.

Molecular imaging of cartilage damage of finger joints in early rheumatoid arthritis with delayed gadolinium-enhanced magnetic resonance imaging.

OBJECTIVE To assess cartilage glycosaminoglycan content and cartilage thickness in the metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis (RA) and healthy volunteers. METHODS After review board approval and informed consent were obtained, 22 subjects were prospectively enrolled (9 patients with early RA [7 women and 2 men with a mean ± SD age of 49 ± 13 years; range 25-68 years] and 13 healthy volunteers [10 women and 3 men with a mean ± SD age of 51 ± 12 years; range 25-66 years). In a total of 44 MCP joints of the index and middle fingers, measurements of cartilage thickness and delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index (T1 [msec]) were obtained using the variable flip-angle method and a 3T MR scanner. MRIs were evaluated for bone edema, erosions, and synovitis (using the RA MRI Scoring criteria). Students t-test was used to test the significance of differences between groups. RESULTS The mean ± SD dGEMRIC index was 497 ± 86 msec in healthy volunteers and was significantly lower in the early RA group (421 ± 76 msec) (P = 0.042). There was no joint space narrowing seen on standard radiographs. No significant difference was found between cartilage thickness in patients with early RA and that in controls (index finger mean ± SD 1.27 ± 0.23 mm in RA patients versus 1.46 ± 0.34 mm in controls [P = 0.16] and middle finger 1.26 ± 0.23 mm in RA patients versus 0.97 ± 0.47 mm in controls [P = 0.10]). No significant correlation was noted between cartilage thickness and dGEMRIC index (R = 0.36, P = 0.88 in RA patients; R = 0.156, P = 0.445 in controls). CONCLUSION Our findings indicate that cartilage damage is present in the MCP joints of patients with early RA despite the absence of joint space narrowing on standard radiographs and MRI. Cartilage damage in RA can be imaged with dGEMRIC.

Feasibility of diffusional kurtosis tensor imaging in prostate MRI for the assessment of prostate cancer: preliminary results.

PURPOSE To assess the feasibility of full diffusional kurtosis tensor imaging (DKI) in prostate MRI in clinical routine. Histopathological correlation was achieved by targeted biopsy. MATERIALS AND METHODS Thirty-one men were prospectively included in the study. Twenty-one were referred to our hospital with increased prostate specific antigen (PSA) values (>4ng/ml) and suspicion of prostate cancer. The other 10 men were volunteers without any history of prostate disease. DKI applying diffusion gradients in 20 different spatial directions with four b-values (0, 300, 600, 1000s/mm(2)) was performed additionally to standard functional prostate MRI. Region of interest (ROI)-based measurements were performed in all histopathologically verified lesions of every patient, as well as in the peripheral zone, and the central gland of each volunteer. RESULTS DKI showed a substantially better fit to the diffusion-weighted signal than the monoexponential apparent diffusion coefficient (ADC). Altogether, 29 lesions were biopsied in 14 different patients with the following results: Gleason score 3+3=6 (n=1), 3+4=7 (n=7), 4+3=7 (n=6), 4+4=8 (n=1), and 4+5=9 (n=2), and prostatitis (n=12). Values of axial (Kax) and mean kurtosis (Kmean) were significantly different in the tumor (Kax 1.78±0.39, Kmean 1.84±0.43) compared with the normal peripheral zone (Kax 1.09±0.12, Kmean 1.16±0.13; p<0.001) or the central gland (Kax 1.40±0.12, Kmean 1.44±0.17; p=0.01 respectively). There was a minor correlation between axial kurtosis (r=0.19) and the Gleason score. CONCLUSION Full DKI is feasible to utilize in a routine clinical setting. Although there is some overlap some DKI parameters can significantly distinguish prostate cancer from the central gland or the normal peripheral zone. Nevertheless, the additional value of DKI compared with conventional monoexponential ADC calculation remains questionable and requires further research.

Pilot study of Iopamidol-based quantitative pH imaging on a clinical 3T MR scanner

ObjectiveThe objective of this study was to show the feasibility to perform Iopamidol-based pH imaging via clinical 3T magnetic resonance imaging (MRI) using chemical exchange saturation transfer (CEST) imaging with pulse train presaturation.Materials and methodsThe pulse train presaturation scheme of a CEST sequence was investigated for Iopamidol-based pH measurements using a 3T magnetic resonance (MR) scanner. The CEST sequence was applied to eight tubes filled with 100-mM Iopamidol solutions with pH values ranging from 5.6 to 7.0. Calibration curves for pH quantification were determined. The dependence of pH values on the concentration of Iopamidol was investigated. An in vivo measurement was performed in one patient who had undergone a previous contrast-enhanced computed tomography (CT) scan with Iopamidol. The pH values of urine measured with CEST MRI and with a pH meter were compared.ResultsIn the measured pH range, pH imaging using CEST imaging with pulse train presaturation was possible. Dependence between the pH value and the concentration of Iopamidol was not observed. In the in vivo investigation, the pH values in the human bladder measured by the Iopamidol CEST sequence and in urine were consistent.ConclusionOur study shows the feasibility of using CEST imaging with Iopamidol for quantitative pH mapping in vitro and in vivo on a 3T MR scanner.