Combined radiotherapy and concurrent tumor treating fields (TTFields) for glioblastoma: Dosimetric consequences on non-coplanar IMRT as initial results from a phase I trial.

BACKGROUND: Glioblastoma is a rapidly proliferating tumor. Patients bear an inferior prognosis with a median survival time of 14-16 months. Proliferation and repopulation are a major resistance promoting factor for conventionally fractionated radiotherapy. Tumor-Treating-Fields (TTFields) are an antimitotic modality applying low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz) alternating electric-fields. More recently interference of TTFields with DNA-damage-repair and synergistic effects with radiotherapy were reported in the preclinical setting. This study aims at examining the dosimetric consequences of TTFields applied during the course of radiochemotherapy. METHODS: Cone-beam-computed-tomography (CBCT)-data from the first seven patients of the PriCoTTF-phase-I-trial were used in a predefined way for dosimetric verification and dose-accumulation of the non-coplanar-intensity-modulated-radiotherapy (IMRT)-treatment-plans as well as geometric analysis of the transducer-arrays by which TTFields are applied throughout the course of treatment. Transducer-array-position and contours were obtained from the low-dose CBCT's routinely made for image-guidance. Material-composition of the electrodes was determined and a respective Hounsfield-unit was assigned to the electrodes. After 6D-fusion with the planning-CT, the dose-distribution was recalculated using a Boltzmann-equation-solver (Acuros XB) and a Monte-Carlo-dose-calculation-engine. RESULTS: Overdosage in the scalp in comparison to the treatment plan without electrodes stayed below 8.5% of the prescribed dose in the first 2 mm below and also in deeper layers outside 1cm2 at highest dose as obtained from dose-volume-histogram comparisons. In the clinical target volume (CTV), underdosage was limited to 2.0% due to dose attenuation by the electrodes in terms of D95 and the effective-uniform-dose. Principal-component-analysis (PCA) showed that the first principal-position-component of the variation of repeated array-placement in the direction of the largest variations and the perpendicular second-component spanning a tangential plane on the skull had a standard deviation of 1.06 cm, 1.23 cm, 0.96 cm, and 1.11 cm for the frontal, occipital, left and right arrays for the first and 0.70 cm, 0.71 cm, 0.79 cm, and 0.68 cm, respectively for the second-principal-component. The variations did not differ from patient-to-patient (p > 0.8, Kruskal-Wallis-tests). This motion led to a diminution of the dosimetric effects of the electrodes. CONCLUSION: From a dosimetric point of view, dose deviations in the CTV due to transducer-arrays were not clinically significant in the first 7 patients and confirmed feasibility of combined adjuvant radiochemotherapy and concurrent TTFields. PriCoTTF Trial: A phase I/II trial of TTFields prior and concomitant to radiotherapy in newly diagnosed glioblastoma. DRKS-ID: DRKS00016667. Date of Registration in DRKS: 2019/02/26. Investigator Sponsored/Initiated Trial (IST/IIT): yes. Ethics Approval/Approval of the Ethics Committee: Approved. (leading) Ethics Committee Nr.: 18-8316-MF, Ethik-Kommission der Medizinischen. Fakultät der Universität Duisburg-Essen. EUDAMED-No. (for studies acc. to Medical Devices act): CIV-18-08-025247.

Radiation dose reduction in CT with adaptive statistical iterative reconstruction (ASIR) for patients with bronchial carcinoma and intrapulmonary metastases.

AIM: To compare the radiation dose and image quality of 64-row chest computed tomography (CT) in patients with bronchial carcinoma or intrapulmonary metastases using full-dose CT reconstructed with filtered back projection (FBP) at baseline and reduced dose with 40% adaptive statistical iterative reconstruction (ASIR) at follow-up. MATERIALS AND METHODS: The chest CT images of patients who underwent FBP and ASIR studies were reviewed. Dose-length products (DLP), effective dose, and size-specific dose estimates (SSDEs) were obtained. Image quality was analysed quantitatively by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurement. In addition, image quality was assessed by two blinded radiologists evaluating images for noise, contrast, artefacts, visibility of small structures, and diagnostic acceptability using a five-point scale. RESULTS: The ASIR studies showed 36% reduction in effective dose compared with the FBP studies. The qualitative and quantitative image quality was good to excellent in both protocols, without significant differences. There were also no significant differences for SNR except for the SNR of lung surrounding the tumour (FBP: 35±17, ASIR: 39±22). DISCUSSION: A protocol with 40% ASIR can provide approximately 36% dose reduction in chest CT of patients with bronchial carcinoma or intrapulmonary metastases while maintaining excellent image quality.

Imaging-Based Liver Function Tests--Past, Present and Future.

UNLABELLED: Preoperative assessment of liver function and prediction of postoperative functional reserve are important in patients scheduled for liver resection. While determination of absolute liver function currently mostly relies on laboratory tests and clinical scores, postoperative remnant liver function is estimated volumetrically using imaging data obtained with computed tomography (CT) or magnetic resonance imaging (MRI). Accurate estimation of hepatic function is also relevant for intensive care patients, oncologic patients, and patients with diffuse liver disease. The indocyanine green (ICG) test is still the only established test for estimating true global liver function. However, more recent tools such as the LiMAx test also allow global assessment of hepatic function. These tests are limited when liver function is inhomogeneously distributed, which is the case in such conditions as unilateral cholestasis or after portal vein embolization. Imaging-based liver function tests were first developed in nuclear medicine and, compared with laboratory tests, have the advantage of displaying the spatial distribution of liver function. Nuclear medicine scans are obtained using tracers such as 99mTc galactosyl and 99mTc mebrofenin. Liver function is typically assessed using planar scintigraphy. However, three-dimensional volumetry is possible with single-photon emission computed tomography (SPECT-CT). Another technique for image-based liver function estimation is Gd-EOB-enhanced MRI. While metabolization of Gd-EOB in the body is similar to that of ICG and mebrofenin, its distribution in the liver can be displayed by MRI with higher temporal and spatial resolution. Moreover, MRI-based determination of liver function can be integrated into routine preoperative imaging. This makes MRI an ideal candidate for preoperative determination of liver function, though the best pulse sequence and the parameter to be derived from the image information remain to be identified. Another question to be answered is how the results may be affected by renal function and the presence of hyperbilirubinemia. As more results from clinical evaluation including comparison with postoperative liver function data become available, image-based liver function tests, especially with use of Gd-EOB as the contrast medium, have the potential to add another dimension to preoperative imaging. KEY POINTS: Liver function consists of a multitude of subfunctions such as biotransformation, excretion and storage. Global liver function tests are score-based tests such as Child-Pugh or MELD as well as the ICG- and LiMAx-test. Imaging-based liver function tests add spatial information. Current clinical standard is the 99mTc-Mebrofenin-scintigraphy. MRI-based function tests with Gd-EOB-DTPA have the potential to integrate seamlessly into clinical workup, feature a higher temporal and spatial resolution and do not rely on ionizing radiation.

Technical note: Influence of the phantom material on the absorbed-dose energy dependence of the EBT3 radiochromic film for photons in the energy range 3 keV-18 MeV.

PURPOSE: Water is the reference medium for radiation therapy dosimetry, but for film dosimetry it is more practical to use a solid phantom. As the composition of solid phantoms differs from that of water, the energy dependence of film exposed within solid phantoms may also differ. The energy dependence of a radiochromic film for a given beam quality Q (energy for monoenergetic beams) has two components: the intrinsic energy dependence and the absorbed-dose energy dependence f(Q), the latter of which can be calculated through a Monte Carlo simulation of radiation transport. The authors used Monte Carlo simulations to study the influence of the phantom material on the f(Q) of the EBT3 radiochromic film (Ashland Specialty Ingredients, Wayne, NJ) for photon beams with energies between 3 keV and 18 MeV. METHODS: All simulations were carried out with the general-purpose Monte Carlo code penelope 2011. The geometrical model consisted of a cylindrical phantom, with the film positioned at different depths depending on the initial photon energy. The authors simulated monoenergetic parallel photon beams and x-ray beams from a superficial therapy system. To validate their choice of simulation parameters, they also calculated f(Q) for older film models, EBT and EBT2, comparing with published results. In addition to water, they calculated f(Q) of the EBT3 film for solid phantom materials commonly used for film dosimetry: RW1 and RW3 (PTW-Freiburg, Freiburg, Germany), Solid Water (Gammex-RMI, Madison, WI), and PMMA. Finally, they combined their calculated f(Q) with published overall energy response data to obtain the intrinsic energy dependence of the EBT3 film in water. RESULTS: The calculated f(Q) for EBT and EBT2 films was statistically compatible with previously published data. Between 10 keV and 18 MeV, the variation found in f(Q) of the EBT3 film for water was within 2.3%, with a standard statistical uncertainty less than 1%. If the quantity dose-to-water in the phantom is considered, which is the common practice in radiation dosimetry, the maximum difference of energy dependence for the solid phantoms with respect to water is about 6%, at an energy of 50 keV. CONCLUSIONS: The EBT3 film shows a reasonably constant absorbed-dose energy dependence when irradiated in water. If the dose-to-water in the phantom is considered, the maximum difference of EBT3 film energy dependence with the solid phantoms studied with respect to water is about 6% (at an energy of 50 keV). The reported overall energy dependence of the EBT3 film in water at energies below 100 keV is mainly due to the intrinsic energy dependence.

Volumetric assessment of optic nerve sheath and hypophysis in idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a headache syndrome characterized by increased CSF pressure. Compression of the hypophysis and distension of the optic nerve sheath are reliable imaging signs. The purpose of the study was to validate, in patients with idiopathic intracranial hypertension, MR imaging-based volumetric measurements of the optic nerve sheath and hypophysis as an objective observation method for more accurate diagnosis and posttreatment follow-up. MATERIALS AND METHODS: Twenty-three patients with idiopathic intracranial hypertension as well as age-, sex-, and body mass index-matched controls underwent volumetric measurements of the optic nerve, optic nerve sheath, and hypophysis on high-resolution T2-weighted MR images by using a 7-cm surface coil, followed by correlation with CSF opening pressures and clinical symptom scores of visual disturbances and headache. RESULTS: Mean values of optic nerve sheath (341.86 ± 163.69 mm(3) versus 127.56 ± 53.17 mm(3), P < .001) and hypophysis volumes (554.59 ± 142.82 mm(3) versus 686.60 ± 137.84 mm(3), P < .05) differed significantly between healthy and diseased subjects. No significant differences between mean optic nerve volumes were observed. Receiver operating characteristic analysis showed optic nerve sheath volumes of >201.30 mm(3) (sensitivity, 86.96%; specificity, 91.30%) and hypophysis volumes of <611.21 mm(3) (sensitivity, 78.26%; specificity, 69.57%) to be indicative of idiopathic intracranial hypertension diagnosis. In patients with idiopathic intracranial hypertension, no correlations were found between optic nerve sheath and hypophysis volumes and CSF opening pressures or clinical scores of visual disturbances and headache. CONCLUSIONS: Semiautomated volumetric measurement of optic nerve sheath and hypophysis has the potential to more accurately diagnose and follow patients with idiopathic intracranial hypertension.

Translating research into licensed vaccines and validated and licensed diagnostic tests.

The USDA Center for Veterinary Biologics (CVB) has the regulatory authority to issue licenses and permits that allow the marketing of pure, safe, potent, and effective veterinary biological products. Under the standard licensing or permitting process, a manufacturer develops, characterizes, and evaluates a product prior to licensure. The CVB evaluates the submitted information, inspects the manufacturing facilities and methods of production and testing, and confirms key product test results through independent testing. This complete and comprehensive evaluation may not be possible during the emergence of a new animal disease or in response to an introduction of a significant transboundary animal disease agent. Processes are in place in the US that allow for more rapid availability of veterinary products in an emerging or emergency animal health situation. But, it can be advantageous to attain preapproval of products prior to their anticipated need. In this article, issues associated with obtaining approval for use of a biological product under emerging or emergency conditions are discussed.

Fast 3D Near-infrared breast imaging using indocyanine green for detection and characterization of breast lesions.

PURPOSE: To evaluate fast 3D near-infrared breast imaging using the optical contrast agent indocyanine green (ICG) for the detection and characterization of breast lesions. MATERIALS AND METHODS: 30 patients with suspicious breast lesions on mammography and/or ultrasound underwent fast 2 Hz 3D optical mammography before, during, and after administration of a 25 mg ICG bolus prior to needle biopsy. The bolus kinetics is analyzed using two perfusion parameters and a derived parameter: "peak amplitude" (PA), "time-to-peak" (TTP) and "peak-time grouped amplitude" (PTA). A receiver operating characteristic curve (ROC) analysis was performed to define a PTA cut-off for reader-independent differentiation of benign and malignant lesions. 8 patients had to be excluded from data analysis. Overall 14 breasts bearing a malignant lesion, 8 breasts bearing a benign lesion and 3 healthy breasts were analyzed. RESULTS: The cut-off-based PTA analysis allowed correct detection for 12 of 14 malignant lesions (tumor size: 8 - 80 mm; sensitivity = 85.7 %). Two malignant lesions were missed. In the benign study group only one fibroadenoma was detected (specificity = 87.5 %). The PTA values differed significantly between the benign group and the malignant group (Mann-Whitney U-test, p < 0.05). Breasts with malignant lesions showed higher peaks at early time-points in ICG perfusion. CONCLUSION: Early perfusion analysis of ICG-enhanced 3D fast optical mammography revealed different enhancement patterns for benign and malignant lesions. This approach might help with the detection of malignant breast lesions and the differentiation from benign lesions.

Olfactory bulb volume and olfactory function in patients with multiple sclerosis.

BACKGROUND: Some studies reported olfactory dysfunction in patients with multiple sclerosis (MS). There is no agreement about the most suitable testing method for measuring olfactory function (OF) in MS patients. Recent studies showed that olfactory bulb volume changes with the degree of olfactory dysfunction. We assessed olfactory bulb volume of MS patients with magnetic resonance imaging (MRI) and related it to the OF. MATERIAL AND METHODS: Volumetric measurements of the right and left olfactory bulb (OB) were performed by manual segmentation within 36 MS patients. Psychophysical testing of the orthonasal OF was performed using threshold-discrimination-identification (TDI) score in MS patients. RESULTS: Of all MS patients, 44.4% displayed olfactory dysfunction. The TDI score of all 36 MS patients, especially the score of the Identification subtest correlated strongly with neurological scores typical of MS. In patients with a decreased OB volume, there was a positive correlation between volumetry of the OB and OF. CONCLUSION: OB volumes may provide valuable information about MS patients with olfactory dysfunction. The TDI test and Identification subtest were very sensitive in detecting olfactory dysfunction in MS patients.

[Pathological changes of the chemosensory function in multiple sclerosis - an MRI study]. / Pathologische Veränderungen der Chemosensorik mittels Kernspintomografie bei Multipler Sklerose - eine MRT-Studie.

PURPOSE: To examine possible causes for olfactory and gustatory dysfunction in MS patients in a prospective study with MRI. MATERIALS AND METHODS: 30 MS patients (21 women, 11 men, 22 - 65 years, Ø 42 years) were examined by MRI. The olfactory bulb (OB) and olfactory brain volume was correlated with the number and volume of MS lesions in the olfactory brain and the non-olfactory brain. Olfactory testing was performed using the Threshold-Discrimination-Identification Test (TDI), and gustatory function was tested using the Taste-Strips-Test (TST). RESULTS: 33 % of the MS patients displayed olfactory dysfunction (8 % of the control group), and 17 % displayed gustatory dysfunction (5 % of the control group). There was a correlation between the olfactory brain volume and the number (r = -0.38, p < 0.05) and volume (r = -0.38, p < 0.05) of MS lesions in the olfactory brain. The olfactory brain volume correlated with the number of MS lesions in the non-olfactory brain (r = -0.48, p < 0.05). The volume of the left OB correlated with the volume of MS lesions in the olfactory brain (r = -0.42, p < 0.05), the number (r = 0.37, p < 0.05) and volume (r = 0.4, p < 0.05) of lesions in the left part of the olfactory brain and with the TST score (r = -0.45, p < 0.05). The TST score correlated with the volume of lesions in the left (r = -0.45, p < 0.05) and right part (r = -0.53, p < 0.05) of the olfactory brain. The TST score correlated with the number of lesions in the non-olfactory brain (r = -0.48, p < 0.05). CONCLUSION: The correlation between a higher number and volume of MS lesions in the olfactory brain with a decreased OB and olfactory brain volume could help to explain olfactory and gustatory dysfunction in MS patients. Just the left OB correlated with the number and volume of lesions in the olfactory brain. Manual segmentation was a suitable method for measuring OB and olfactory brain volume.

[Dynamic contrast-enhanced MRI of the prostate: comparison of two different post-processing algorithms]. / Dynamische kontrastmittelunterstützte MRT der Prostata: Vergleich von zwei Auswerteverfahren.

PURPOSE: To evaluate the usefulness of a commercially available post-processing software tool for detecting prostate cancer on dynamic contrast-enhanced magnetic resonance imaging (MRI) and to compare the results to those obtained with a custom-made post-processing algorithm already tested under clinical conditions. MATERIALS AND METHODS: Forty-eight patients with proven prostate cancer were examined by standard MRI supplemented by dynamic contrast-enhanced dual susceptibility contrast (DCE-DSC) MRI prior to prostatectomy. A custom-made post-processing algorithm was used to analyze the MRI data sets and the results were compared to those obtained using a post-processing algorithm from In vivo Corporation (Dyna CAD for Prostate) applied to dynamic T 1-weighted images. Histology was used as the gold standard. RESULTS: The sensitivity for prostate cancer detection was 78 % for the custom-made algorithm and 60 % for the commercial algorithm and the specificity was 79 % and 82 %, respectively. The accuracy was 79 % for our algorithm and 77.5 % for the commercial software tool. The chi-square test (McNemar-Bowker test) yielded no significant differences between the two tools (p = 0.06). CONCLUSION: The two investigated post-processing algorithms did not differ in terms of prostate cancer detection. The commercially available software tool allows reliable and fast analysis of dynamic contrast-enhanced MRI for the detection of prostate cancer.

Dependence of renal blood flow on renal artery stenosis measured using CT angiography.

PURPOSE: The present study investigates the suitability of computed tomography angiography (CTA) depicting the degree of renal artery stenosis for estimating renal blood flow (RBF) in a kidney. MATERIALS AND METHODS: We investigated renal artery stenosis assessment by CTA in eight adult female hybrid pigs with an ultrasound probe implanted at the renal vein for RBF measurement. An inflatable metal-free cuff was placed around the renal artery to control the RBF. The RBF was then reduced in four steps. For each reduced RBF value and baseline RBF, CTA with a reconstructed slice thickness of 0.625 mm was performed in the arterial phase following injection of 80 ml of nonionic intravenous contrast medium. The radius of the stenotic and non-stenotic renal artery segment was measured in the reconstructed images. RESULTS: A significant linear correlation (p < 0.0001) was found between the relative apparent stenosis (calculated as the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment) and RBF. The linear regression yielded a slope of 0.57 and a y-axis of 24.1 %. A significant linear correlation (p < 0.0001) was also found between the relative true stenosis (the ratio of the radii of the actual stenotic segment and a non-stenotic renal artery segment at baseline) and the RBF. The linear regression yielded a slope of 0.67 and a y-axis of 13.8 %. CONCLUSION: The results show that the relative stenosis apparent on CTA differs from the true degree of renal artery stenosis. Nevertheless, the degree of renal artery stenosis determined by CTA provides a reliable estimate of the resulting RBF reduction.

Use of H(2) (15)O-PET for investigating perfusion changes in pelvic tumors due to regional hyperthermia.

PURPOSE: An increase in tumor oxygenation and perfusion due to hyperthermia has been reported for experimental tumors. The present study was performed to investigate this hypothesis in patients who underwent regional hyperthermia. METHODS: Twenty-seven patients with primary or recurrent pelvic tumors were included in this study. Prior to and up to 1 h after regional hyperthermia, perfusion and partition coefficient were quantitatively determined by utilizing H(2) (15)O-PET. First pass PET images were fused with the segmented common iliac artery from separately acquired CT scan. The arterial input function was extracted from the common iliac arteries using the dynamic PET images and the fused CT. The fused images were also used to extract tumor activity-time curves. Perfusion was calculated from the total tumor curves with correction for arterial spill-over. Changes in perfusion and partition coefficient were analyzed and correlated with various treatment parameters. RESULTS: Heating under hyperthermia conditions significantly increased the partition coefficient for pelvic tumors (P = 0.005). The increase correlated with the duration of hyperthermia and was found in patients treated for more than 1 h and persisted for more than 1 h after the end. Significant changes in perfusion were not observed. Perfusion had recurred to initial values 20 min after heating. CONCLUSIONS: The increase in partition coefficient reflects an increased diffusion distance of radio-labeled water. Therefore water diffusion is increased due to hyperthermia. Analogous to water diffusion, the diffusion of inert gases is also facilitated, improving the oxygenation of hypoxic tumor cells. Our results suggest that tumor oxygenation can probably be enhanced by regional hyperthermia for a period of more than 1 h after heating, provided hyperthermia is applied for at least 60 min. The effect was observed to be reversible within one week.

[Pharmacokinetic MRI of the prostate: parameters for differentiating low-grade and high-grade prostate cancer]. / Pharmakokinetische MRT der Prostata: Parameter zur Unterscheidung von Low-grade- und High-grade-Prostatakarzinomen.

PURPOSE: To investigate whether pharmacokinetic MRI parameters "perfusion, blood volume, mean transit time (MTT), interstitial volume, permeability, extraction coefficient, delay, and dispersion" allow the differentiation of low-grade (Gleason score < or = 6) and high-grade (Gleason score > or = 7) prostate cancer. MATERIALS AND METHOD: Forty-two patients with prostate cancer verified by biopsy (PSA 2.7 to 31.4 ng/ml) and scheduled for prostatectomy underwent MRI at 1.5 Tesla using the dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence (temporal resolution, 1.65 s) and a combined endorectal body phased array coil. Parametric maps were computed using a sequential 3-compartment model and the corresponding post-processing algorithms. A total of 41 areas of prostate cancer (15 low-grade, 26 high-grade cancers) in 32 patients were able to be correlated with the prostatectomy specimens and were included in the analysis. RESULTS: Low-grade prostate cancers had a higher mean blood volume (1.76 % vs. 1.64 %, p = 0.039), longer MTT (6.39 s vs. 3.25 s, p < 0.001), and lower mean permeability (2.57 min (-1) vs. 3.86 min (-1), p = 0.011) than high-grade cancers. No statistically significant difference was found for perfusion (p = 0.069), interstitial volume (p = 0.849), extraction coefficient (p = 0.615), delay (p = 0.489), and dispersion (p = 0.306). CONCLUSIONS: Blood volume, MTT, and permeability allow the differentiation of low-grade and high-grade prostate cancer. They may be used to detect cancer progression by MRI in patients managed by active surveillance.

Muscle and nerve pathology in Dunnigan familial partial lipodystrophy.

OBJECTIVE: To characterize muscle and nerve pathology in Dunnigan familial partial lipodystrophy (FPLD). METHODS: We used conventional histology, immunohistochemistry, messenger RNA (mRNA) expression, gene sequencing, and clinical studies of 13 patients with neuromuscular involvement. RESULTS: The clinical findings consisted of muscle hypertrophy (12/13), severe myalgias (9/13), and multiple nerve entrapment syndromes (8/13). Skeletal muscle histology demonstrated marked Type 1 and 2 muscle fiber hypertrophy and nonspecific myopathic changes, whereas numerous paranodal myelin swellings (tomacula) were found in sural nerve biopsies. We found that myostatin mRNA expression was reduced in patients with FPLD vs controls. We sequenced the myostatin gene in our subjects, but found no mutations. We then investigated whether or not SMAD, the intracellular mediator of myostatin signaling, might be impaired in patients with FPLD. We found that in FPLD muscle, a large number of SMAD molecules adhered to the nuclear membrane and were not found within the nucleus, compared with normal muscle or muscle from a patient with a non-FPLD lamin A/C disease. CONCLUSION: The myopathy and neuropathy associated with Dunnigan familial partial lipodystrophy are distinct from other lamin A/C disorders. We hypothesize that the lipodystrophy-associated mutation interferes with SMAD signaling, linking this type of lipodystrophy to the phenotypically similar myostatin deficiency.

Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction.

Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 +/- 52.0%) and lower partition coefficients (-31.6 +/- 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.

Glioma assessment using quantitative blood volume maps generated by T1-weighted dynamic contrast-enhanced magnetic resonance imaging: a receiver operating characteristic study.

PURPOSE: To investigate the use of blood volume maps in the non-invasive separation of glioma grades. MATERIAL AND METHODS: T1-weighted quantitative dynamic contrast-enhanced magnetic resonance imaging was used to quantify the fractional intratumoral blood volume of 41 gliomas (World Health Organization (WHO) grades II-IV). Two methods, mean fractional intratumoral blood volume determination and a system based on thresholds for extracting the tumor pixels with the highest vascularization from the blood volume maps, were investigated by means of receiver operating characteristic (ROC) analysis. The thresholds were adjusted using the ROC curve area calculated using the trapezoid method. RESULTS: The ability to separate grade II (WHO) gliomas from grades III-IV was nearly the same for both methods (ROC curve area 0.941 (threshold) versus 0.932 (mean value)) and significantly greater than the ability to separate grade IV (WHO) gliomas from grades II-III (ROC curve area 0.792 (threshold) versus 0.787 (mean value)). The best correspondence with WHO glioma grading was achieved using thresholds corresponding to only the 5.2% of tumor voxels with the largest blood volume for separating grade II gliomas and 4% for separating grade IV gliomas. CONCLUSION: Use of the optimized threshold resulted in matching with the WHO grading system in 74% of cases.

Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI.

PURPOSE: To differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. MATERIAL AND METHODS: Tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. RESULTS: Axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm(3). In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420 % (p < 0.001) and 424 % (p < 0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. CONCLUSION: The results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model.

Bedside microdialysis reflects dysfunction of cerebral energy metabolism in patients with aneurysmal subarachnoid hemorrhage as confirmed by 15 O-H2 O-PET and 18 F-FDG-PET.

OBJECTIVE: To compare microdialysis (MD) and positron emission tomography (PET) in the detection of ischemia in aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS: 15 SAH patients (13F/2M, 48+/-13 years, WFNS Grade I-V) were prospectively included in the study. A MD-catheter was inserted into the brain parenchyma most likely to be affected by vasospasm directly after aneurysm clipping. Glucose, pyruvate, lactate, glutamate and glycerol were analyzed hourly (CMA 600). 15O-H2O-PET scans (n=10) and 18F-FDG-PET scans (n=13) were performed between the day 2 and 17 after SAH. 15O-H2O-PET data were merged with CT scans to provide quantification of rCBF within the MD-ROI (rCBFMD; Amira, ZIB Berlin, Germany). 18F-FDG-PET data were evaluated visually by visual analysis. RESULTS: Regions of glucose hypometabolism were observed in 10 patients with symptoms of ischemia. Their rCBF was lower compared to asymptomatic patients (p<0.05). The MD levels of glutamate, lactate, the L/P ratio and glycerol were significantly higher in symptomatic than asymptomatic patients (p<0.05). Out of all measured MD parameters, glutamate showed the closest correlation with rCBF (r=-0.66, p=0.014). Microdialysis parameters were well correlated with glucose hypometabolism (18F-FDG-PET) and symptoms of ischemia. However, the threshold for a metabolic derangement was above the limits of cerebral ischemia defined by PET. CONCLUSION: MD is a useful tool to monitor ischemia, especially in patients with high-grade SAH.

Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients.

72 consecutive patients with suspected parkinsonian syndromes (PS) were studied by dopamine transporter (DAT) and D2 receptor SPECT in order to evaluate the accuracy of combined SPECT imaging. In the follow-up, the patients were diagnosed as having Parkinson's disease (PD, n = 25), dementia with Lewy bodies (DLB, n = 6), multiple system atrophy (MSA, n = 13), progressive supranuclear palsy (PSP, n = 8), corticobasal degeneration (CBD, n = 9), and essential tremor (ET, n = 11). Using the iteratively estimated optimal cutoffs, DAT was reduced in 57/61 PS patients, whereas all ET patients were identified as "normal". Reduced D2 receptor binding had 7/13 patients with MSA, 6/8 patients with PSP, 2/9 patients with CBD and no ET, PD or DLB patients. FP-CIT SPECT allows an accurate detection of nigrostriatal affection in neurodegenerative PS. IBZM SPECT is useful to approve the diagnosis of PSP and MSA although a normal finding cannot exclude an atypical PS. IBZM SPECT seems to be of restricted value in CBD.

Regional pelvic hyperthermia as an adjunct to chemotherapy (oxaliplatin, folinic acid, 5-fluorouracil) in pre-irradiated patients with locally recurrent rectal cancer: a pilot study.

The aim of this study was to evaluate the feasibility and toxicity of a novel hyperthermic chemotherapy approach for patients with locally recurrent adenocarcinoma of the rectum. All patients were pre-irradiated (> or = 45 Gy) and had histologically proven pelvic recurrence. Hyperthermic chemotherapy was applied according to a modified 'OFF'-schedule with weekly infusions of 43 mg/m2 of oxaliplatin (i.v., 120 min), 500 mg/m2 of folinic acid (i.v., 120 min) and 2.6 g/m2 of continuous infusional 5-fluorouracil (24 h) for 6 consecutive weeks. Oxaliplatin was started in parallel to pelvic radiofrequency hyperthermia that was provided by the BSD 2000-system. A total of 67 applications were administered to nine patients and were well tolerated. A total of 55/67 (82%) chemotherapy courses were applied without dose-reduction. In 62/67 (93%) hyperthermia sessions, a treatment time of > 60 min was maintained. Tolerated power levels were on average 600 W and, thus, slightly lower than those described in curative pelvic hyperthermia schedules. Eight out of 10 episodes of severe (WHO III degrees) toxicity represented typical side-effects of the chemotherapy given (nausea n = 4, diarrhoea n = 3, neuropathy n = 1). Two severe adverse events were firstly attributable to hyperthermia (haematuria, n = 1; deterioration of a decubital ulcer, n = 1). No patient suffered WHO-disease progression during the treatment period. Two patients achieved a partial remission. It is concluded that hyperthermic chemotherapy with oxaliplatin, folinic acid and 5-FU is feasible on an outpatient basis. Overall toxicity was moderate, although hyperthermia may add side-effects to this approach. Results, moreover, suggest a relevant palliative effect in patients with pre-irradiated pelvic recurrence of rectal cancer.