Lutz Lüdemann

Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage A Correlative Microdialysis-PET Study

Background and Purpose— Cerebral microdialysis (MD) is discussed as a technique for detection of cerebral ischemia in subarachnoid hemorrhage; however, clinical data on cerebral blood flow (CBF) are limited in these patients. The main objective of this study was to investigate whether pathological MD parameters reflect a reduced regional CBF (rCBF) determined by 15O-H2O PET. Methods— Thirteen subarachnoid hemorrhage patients (age, 48.7±15.0 years; World Federation of Neurological Surgeons grade 1 to 5) were studied. Extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol levels were analyzed hourly. rCBF was determined in the volume of interest of the MD catheter and all vascular territories. MD values were correlated to rCBF on the day of PET. Then, MD concentrations of asymptomatic versus ischemic phases (3-day medians) were analyzed. Results— In symptomatic patients (n=10), rCBF was significantly lower compared with controls (n=3, P =0.048). Glutamate correlated best with rCBF (r =−0.66; P =0.014), followed by glycerol (r =−0.62; P =0.021). The L/P ratio was most sensitive (0.82) and specific (1.0) in indicating symptoms of ischemia, but only during longer periods of ischemia. Conclusions— rCBF correlates best with glutamate, followed by glycerol, whereas the L/P ratio is sensitive only after longer periods of ischemia. Clinically relevant regional metabolic derangements occur already above an rCBF of 20 mL·100 g−1·min−1. Future research should focus on identifying alternative causes of metabolic derangement in subarachnoid hemorrhage patients and optimal treatment management in these patients.

Pharmacokinetic analysis of glioma compartments with dynamic Gd-DTPA-enhanced magnetic resonance imaging

Dynamic contrast-enhanced magnetic resonance imaging (MRI) is widely used for measuring perfusion and blood volume, especially cerebral blood volume (CBV). In case of blood-brain barrier (BBB) disruption, the conventional techniques only partially determine the pharmacokinetic parameters of contrast medium (CM) exchange between different compartments. Here a modified pharmacokinetic model is applied, which is based on the bidirectional CM exchange between blood and two interstitial compartments in terms of the fractional volumes of the compartments and the vessel permeabilities between them. The evaluation technique using this model allows one to quantify the fractional volumes of the different compartments (blood, cells, slowly and fast enhancing interstitium) as well as the vessel permeabilities and cerebral blood flow (CBF) with a single T1-weighted dynamic MRI measurement. The method has been successfully applied in 25 glioma patients for generating maps of all of these parameters. The fractional volume maps allow for the differentiation of glioma vascularization types. The maps show a good correlation with the histological grading of these tumors. Furthermore, regions with enhanced interstitial volumes are found in high-grade gliomas. Differences in permeability maps of Gd-DTPA apart from BBB disruption do not exist between different tissue types. CBF measured in high-grade glioma is less pronounced than it would be expected from their blood volume. Therefore pharmacokinetic imaging provides an additional tool for glioma characterization.

Comparison of dynamic contrast-enhanced MRI with WHO tumor grading for gliomas

Abstract.Assessment of vascular proliferation as an important grading criterion has been employed in both the histologic and the radiologic characterization of gliomas with encouraging results. Perfusion in gliomas can be measured by dynamic contrast-enhanced magnetic resonance imaging (dMRI). The goal of this study was to develop a model for simultaneously quantifying the fractional volumes of different tissue compartments of gliomas by dMRI. A modified method for evaluating dynamic contrast-enhanced MR images is presented which simultaneously determines the fractional vascular, interstitial, and cellular volumes of gliomas. This method differs from techniques used in other studies in that it is based on a three-compartment model: a single blood compartment and two interstitial ones. The fractional volume maps are compared with the WHO glioma grading. The results show the method to be feasible. Using cerebral blood volume (CBV), dMRI grading showed a correspondence with WHO grading in 83% of the cases (20/24 gliomas WHO grades II–IV). The use of interstitial volume maps can also be helpful, for instance, in differentiating gliomas from other brain tumors. As a supplement to conventional MRI, dynamic MR techniques thus provide a useful tool for improving in vivo glioma characterization.

Evaluation of normal prostate tissue, chronic prostatitis, and prostate cancer by quantitative perfusion analysis using a dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence.

Objective:To quantify independent pharmacokinetic parameters for differentiation of prostate pathology. Material and Methods:Twenty-seven patients with biopsy-proven prostate cancer (PSA: 1.4–16.1 ng/mL) underwent magnetic resonance imaging with a new dynamic contrast-enhanced, inversion-prepared dual-contrast gradient echo sequence (T1/T2*-weighted, 1.65 seconds temporal resolution) using a combined endorectal/body phased-array coil at 1.5 Tesla. Perfusion, blood volume, mean transit time, delay, and dispersion were calculated using a sequential 3-compartment model. Twenty-three patients underwent prostatectomy. For histologic correlation a pathologist mapped areas of normal prostate tissue, chronic prostatitis, and prostate cancer (total of 63 areas) on histologic sections corresponding to the magnetic resonance imaging planes. Results:Compared with normal prostate tissue, low-grade cancer (Gleason score ≤6) only showed higher perfusion (1.01 mL/cm3/min vs. 0.26 mL/cm3/min, P = 0.050), whereas high-grade cancer showed higher perfusion (1.21 mL/cm3/min vs. 0.26 mL/cm3/min, P ≤ 0.001), higher blood volume (1.44% vs. 0.95%, P = 0.005), shorter mean transit time (3.55 seconds vs. 4.40 seconds, P = 0.019), shorter delay (10.15 seconds vs. 13.36 seconds, P = 0.015), and smaller dispersion (8.56 seconds vs. 12.11 seconds, P = 0.020). High-grade cancer showed higher perfusion than chronic prostatitis (1.21 mL/cm3/min vs. 0.90 mL/cm3/min, P = 0.041). Chronic prostatitis showed higher perfusion (0.90 mL/cm3/min vs. 0.26 mL/cm3/min, P = 0.006), higher blood volume (1.53% vs. 0.95%, P = 0.046), shorter delay (11.42 seconds vs. 13.36 seconds, P = 0.015), and smaller dispersion (10.49 seconds vs. 12.11 seconds, P = 0.020) than normal prostate tissue. There were no statistically significant differences between low-grade and high-grade cancer or between low-grade cancer and chronic prostatitis. Conclusion:The pharmacokinetic parameters investigated, especially perfusion, allow statistically significant in situ differentiation of normal prostate tissue from cancer and chronic prostatitis and of high-grade cancer from chronic prostatitis.

Breast cancer: early- and late-fluorescence near-infrared imaging with indocyanine green--a preliminary study.

PURPOSE To assess early- and late-fluorescence near-infrared imaging, corresponding to the vascular (early-fluorescence) and extravascular (late-fluorescence) phases of indocyanine green (ICG) enhancement, for breast cancer detection and benign versus malignant breast lesion differentiation. MATERIALS AND METHODS The study was approved by the ethical review board; all participants provided written informed consent. Twenty women with 21 breast lesions were examined with near-infrared imaging before, during, and after intravenous injection of ICG. Absorption and fluorescence projection mammograms were recorded simultaneously on a prototype near-infrared imaging unit. Two blinded readers independently assessed the images and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence mammograms. Imaging results were compared with histopathologic findings. Lesion contrast and diameter on the fluorescence mammograms were measured, and Cohen κ, Mann-Whitney U, and Spearman ρ tests were conducted. RESULTS The absorption-corrected fluorescence ratio mammograms showed high contrast (contrast value range, 0.25-0.64) between tumors and surrounding breast tissue. Malignant lesions were correctly defined in 11 (reader 1) and 12 (reader 2) of 13 cases, and benign lesions were correctly defined in six (reader 1) and five (reader 2) of eight cases with late-fluorescence imaging. Lesion visibility scores for malignant and benign lesions were significantly different on the fluorescence ratio mammograms (P = .003) but not on the absorption mammograms (P = .206). Mean sensitivity and specificity reached 92% ± 8 (standard error of mean) and 75% ± 16, respectively, for fluorescence ratio imaging compared with 100% ± 0 and 25% ± 16, respectively, for conventional mammography alone. CONCLUSION Preliminary data suggest that early- and late-fluorescence ratio imaging after ICG administration can be used to distinguish malignant from benign breast lesions.

Brain tumor perfusion: Comparison of dynamic contrast enhanced magnetic resonance imaging using T1, T2, and T 2 * contrast, pulsed arterial spin labeling, and H215O positron emission tomography

OBJECTIVES Different techniques for measuring of perfusion are clinically available, but these are usually applied to healthy brain tissue. MATERIAL AND METHODS Five different techniques were used here in 12 patients with brain tumors to investigate the impact of tumor vascularization on the perfusion signal: three qualitative dynamic contrast-enhanced/susceptibility-contrast magnetic resonance imaging (DCE-MRI/DSC-MRI) techniques exploiting T(1), T(2), T(2)(*) contrast, and two quantitative techniques, pulsed arterial spin labeling (PASL) and H(2)(15)O positron emission tomography (H(2)(15)O-PET). RESULTS In a first approximation, a linear correlation was found between all five imaging modalities regarding the perfusion signal of both, normal brain tissue and tumor. The estimated values for tumor perfusion differed significantly between the techniques (1=methodical mean in arbitrary units): PASL: 0.83, H(2)(15)O-PET: 0.62, T(1)-DCE: 1.73, T(2)-DCE: 0.69, T(2)(*)-DSC: 0.89. CONCLUSIONS The tumor perfusion values, determined with different techniques are not comparable. The T(2)(*)-DSC, here applied with contrast agent presaturation of extravascular space, and PASL depict median perfusion most reliably.

DIFFERENCES IN SUPRATENTORIAL DAMAGE OF WHITE MATTER IN PEDIATRIC SURVIVORS OF POSTERIOR FOSSA TUMORS WITH AND WITHOUT ADJUVANT TREATMENT AS DETECTED BY MAGNETIC RESONANCE DIFFUSION TENSOR IMAGING

PURPOSE To elucidate morphologic correlates of brain dysfunction in pediatric survivors of posterior fossa tumors by using magnetic resonance diffusion tensor imaging (DTI) to examine neuroaxonal integrity in white matter. PATIENTS AND METHODS Seventeen medulloblastoma (MB) patients who had received surgery and adjuvant treatment, 13 pilocytic astrocytoma (PA) patients who had been treated only with surgery, and age-matched healthy control subjects underwent magnetic resonance imaging on a 3-Tesla system. High-resolution conventional T1- and T2-weighted magnetic resonance imaging and DTI data sets were obtained. Fractional anisotropy (FA) maps were analyzed using tract-based spatial statistics, a part of the Functional MRI of the Brain Software Library. RESULTS Compared with control subjects, FA values of MB patients were significantly decreased in the cerebellar midline structures, in the frontal lobes, and in the callosal body. Fractional anisotropy values of the PA patients were not only decreased in cerebellar hemispheric structures as expected, but also in supratentorial parts of the brain, with a distribution similar to that in MB patients. However, the amount of significantly decreased FA was greater in MB than in PA patients, underscoring the aggravating neurotoxic effect of the adjuvant treatment. CONCLUSIONS Neurotoxic mechanisms that are present in PA patients (e.g., internal hydrocephalus and damaged cerebellar structures affecting neuronal circuits) contribute significantly to the alteration of supratentorial white matter in pediatric posterior fossa tumor patients.

Prostate MR Imaging: Tissue Characterization with Pharmacokinetic Volume and Blood Flow Parameters and Correlation with Histologic Parameters

PURPOSE To prospectively determine whether pharmacokinetic magnetic resonance (MR) imaging parameters correlate with histologic mean vessel density (MVD), mean vessel area (MVA), and mean interstitial area (MIA) and whether these parameters enable differentiation of prostate cancer, chronic prostatitis, and normal prostate tissue. MATERIALS AND METHODS This study was approved by the institutional review board, and informed consent was obtained from all patients. Thirty-five patients with biopsy-proved prostate cancer were examined with a dynamic contrast material-enhanced inversion-prepared dual-contrast gradient-echo sequence (temporal resolution, 1.65 seconds) at 1.5 T to calculate blood volume, interstitial volume, and blood flow. These parameters were correlated with MVD, MVA, and MIA in 95 areas (prostate cancer, n = 36; chronic prostatitis, n = 27; normal prostate tissue, n = 32). For each MR area, five 1-mm(2) squares (original magnification, x100) of the matching histologic area were analyzed. The Wilcoxon signed-rank test was used for statistical analysis. RESULTS Blood volume correlated poorly with MVD (Spearman correlation coefficient, 0.252; P = .014) but did not correlate at all with MVA (P = .759). Interstitial volume did not correlate with MIA (P = .507). Blood volume differed between patients with prostate cancer and those with a normal prostate (1.49% vs 0.84%, respectively; P < .001). Interstitial volume differed between patients with chronic prostatitis and those with a normal prostate (39.00% vs 22.59%, respectively; P = .022). Blood flow differed between patients with prostate cancer and those with a normal prostate (0.97 mL/[cm(3) x min(-1)] vs 0.34 mL/[cm(3) x min(-1)], respectively; P < .001), between patients with prostate cancer and those with chronic prostatitis (0.97 mL/[cm(3) x min(-1)] vs 0.60 mL/[cm(3) x min(-1)], respectively; P = .026), and between patients with chronic prostatitis and those with a normal prostate (0.60 mL/[cm(3) x min(-1)] vs 0.34 mL/[cm(3) x min(-1)], respectively; P = .023). CONCLUSION Blood volume and interstitial volume did not reliably correlate with the histologic parameters. Only blood flow enabled differentiation of prostate cancer, chronic prostatitis, and normal prostate tissue.

BOLD signal in the motor cortex shows a correlation with the blood volume of brain tumors

To investigate whether and how the blood‐oxygenation‐level–dependent (BOLD) functional MRI (fMRI) signal is modified by brain tumors.

Non-invasive magnetic resonance thermography during regional hyperthermia

Regional hyperthermia is a non-invasive technique in which cancer tissue is exposed to moderately high temperatures of approximately 43–45°C. The clinical delivery of hyperthermia requires control of the temperatures applied. This is typically done using catheters with temperature probes, which is an interventional procedure. Additionally, a catheter allows temperature monitoring only at discrete positions. These limitations can be overcome by magnetic resonance (MR) thermometry, which allows non-invasive mapping of the entire treatment area during hyperthermia application. Various temperature-sensitive MRI parameters exist and can be exploited for MR temperature mapping. The most popular parameters are proton resonance frequency shift (PRFS) (Δφ corresponding to a frequency shift of 0.011 ppm, i.e. 0.7 Hz per °C at 1.5 Tesla), diffusion coefficient D (ΔD/D = 2–3 % per °C), longitudinal relaxation time T1 ( per °C), and equilibrium magnetisation M0 ( per °C). Additionally, MRI temperature mapping based on temperature-sensitive contrast media is applied. The different techniques of MRI thermometry were developed to serve different purposes. The PRFS method is the most sensitive proton imaging technique. A sensitivity of ±0.5°C is possible in vivo but use of PRFS imaging remains challenging because of a high sensitivity to susceptibility effects, especially when field homogeneity is poor, e.g. on interventional MR scanners or because of distortions caused by an inserted applicator. Diffusion-based MR temperature mapping has an excellent correlation with actual temperatures in tissues. Correct MR temperature measurement without rescaling is achieved using the T1 method, if the scaling factor is known. MR temperature imaging methods using exogenous temperature indicators are chemical shift and 3D phase sensitive imaging. TmDOTMA− appears to be the most promising lanthanide complex because it showed a temperature imaging accuracy of <0.3°C.