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Biomedical subjects

J Debus

Publications and source records attributed to J Debus.

154 records · Page 9Linked to original sources

Improved target volume definition for precision radiotherapy planning of meningiomas by correlation of CT and dynamic, Gd-DTPA-enhanced FLASH MR imaging.

In this methodological paper the authors report a fast, T1-weighted gradient-echo sequence (FLASH) for dynamic, Gd-DTPA-enhanced magnetic resonance (MR) imaging of meningiomas and its application in precision radiotherapy planning. Indications for radiotherapy included unresected tumors, tumor remaining after surgery, and recurrences. The patient's head was fixed in a stereotactic localization system which is usable at the CT, MR and the linear accelerator installations. By phantom measurements different materials (steel, aluminum, titanium, plastic, wood, ceramics) used for the stereotactic system were tested for mechanical stability and geometric MR image distortion. All metallic stereotactic rings (closed rings made of massive metal) led to a more or less dramatic geometric distortion and signal cancellation in the MR images. The best properties--nearly no distortion and high mechanic stability--are provided by a ceramic ring. If necessary, the remaining geometric MR image distortion can be 'corrected' (reducing displacements to the size of a pixel) by calculations based on modeling the distortion as a fourth order two-dimensional polynomial. The target volume was defined in dynamic, T1-weighted FLASH MR images, which were measured before, during, and after the controlled intravenous infusion of 0.1 mmol/kg body weight Gd-DTPA. The stereotactic localization technique allows the precise transfer of the target volume information from MR onto CT data to provide a map of the radiation attenuation coefficient for dose calculation. In genera, the superior soft tissue contrast of MR showed an excellent tumor delineation, especially in regions, such as the base of the skull, where the target often was obscured in CT images.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

In vivo detection of ultrasonically induced cavitation by a fibre-optic technique.

The measurement of cavitation events in tissue in vivo would greatly assist us to better understand how pulsed high energy ultrasound (PHEUS) interacts with living tissues, especially with regard to cancer therapy. To accomplish this, we designed and built a fibre-optic hydrophone. The principle was to couple the light of a laser diode into a lightfibre and to register the ultrasound induced modification of the refractive index in tissue. In this manner, the cavitation event could be quantitatively investigated both in water and in vivo. The structure of the bubble dynamic is in reasonable agreement with theoretical predictions, and in vitro measurements. With the fibre-optic set-up, the pressure signal can also be detected. PHEUS was generated by an electromagnetic source adapted from a commercial lithotripter (Lithostar Siemens). As biological tissue we used the experimental R3327-AT1 Dunning prostate tumor growing subcutaneously in the thigh of male Copenhagen rats. The lifetime of the cavitation bubble in water increased with the energy level of the ultrasonic pulse from 250 microseconds at 13 kV capacitor voltage to 750 microseconds at 21 kV, while the lifetime inside the tumor tissue in vivo increased only from 100 microseconds at 13 kV to 220 microseconds at 21 kV capacitor voltage.

Animals↗

[TOF-MR angiography in radiotherapy treated cerebral arteriovenous malformations].

Intracerebral arteriovenous malformations represent congenital anomalies with an arteriovenous shunt (nidus). The therapeutic goal is to eliminate the risk of bleeding and to improve the clinical symptoms. The exact localization of the nidus and the identification of the feeding arteries are critical for therapy planning. Up to now conventional brain angiograms have been used for treatment planning and for the assessment of therapy response. We studied whether 3D time-of-flight (TOF) MR angiography can be used for therapy planning and monitoring. MRI and TOF-MRA studies of 28 patients undergoing radiotherapy were evaluated. They were compared to conventional angiography to assess the MRA study. A Correct identification of the arterial feeder and the nidus was possible in about 75% of the patients. In combination with the MRI study, an important 3D dataset for treatment planning could be obtained that includes therapeutically relevant information on the localization and spatial structure of the AVM as well as the adjacent brain tissue. As a noninvasive technique, close-meshed follow-up studies could be performed with MRA.

Adolescent↗

Fractionated stereotactically guided radiotherapy of head and neck tumors: a report on clinical use of a new system in 195 cases.

Between November 1988 and December 1992, 195 patients with tumors of the head and neck (low grade gliomas, meningiomas, neurinomas, chordomas and miscellaneous) were treated with a newly developed stereotactical system for fractionated, conformal, high-precision radiotherapy. The overall preparation time, including head mask production for fixation, CT, MRI, 3-D treatment planning and stereotactical localisation could be reduced to 4-5 h per patient. The use of MR in the target definition was increased to a mean of about 60%. The medial follow-up time is 22 months. Three different patient groups were selected according to pretreatment. Patients with full high-precision radiotherapy survived in 95% of cases, patients with boost treatment in 86% and patients with preirradiated recurrent disease in 64%. Meningiomas as the largest histology group (n = 62) showed partial response in 27% and complete response in 10% of cases. Progression occurred in two patients. All patients are alive. Acute side-effects were minimal and of the order of 10%, no late complications occurred despite tumor doses ranging up to 72 Gy. High-precision radiotherapy as it is performed in Heidelberg can be regarded as an effective, reliable and tolerable system for selected tumors of the head and neck.

Adolescent↗

Treatment of the Dunning prostate rat tumor R3327-AT1 with pulsed high energy ultrasound shock waves (PHEUS): growth delay and histomorphologic changes.

We are interested in the interaction of pulsed high energy shock waves (PHEUS) on soft tissues treated in situ to evaluate its potential for therapeutic use. The experimental apparatus built by us was adapted from a lithotripter designed for clinical use. For the present studies we used the R3327-AT1 Dunning prostate tumor growing s.c. in the thigh of Copenhagen rats. The treatments consisted of four groups of eight animals each who received 500 or 2000 pulses at 1 or 5 Hz. Sham-treated tumor bearing animals served as controls (n = 11). During each PHEUS treatment, petechial bleeding of the skin at the point of entry and exit of sound appeared. Sonication at a repetition rate of five Hz seemed to induce more macroscopic damage in terms of hematomas and skin effects. The cytotoxic effects of PHEUS to tumor tissue were sufficient to induce a significant delay (p less than 0.05) in tumor growth but no clear-cut dose relationship was established. Histological studies revealed widespread early rupture of the fine vasculature with extravasation of erythrocytes. By 72 hr., in PHEUS treated tumors, a large necrosis was seen within the central zone which was never observed in sham-treated tumors. Our results clearly indicate that PHEUS has a cytotoxic potential. The observation of a rapid onset of hemostasis, stark hemorrhage and necrosis in the treatment field would suggest that vascular damage is an important contributing factor.

Animals↗

Pharmacokinetic MRI for assessment of malignant glioma response to stereotactic radiotherapy: initial results.

The purpose of this study was to assess the value of dynamic, contrast-enhanced MRI in patients with malignant glioma (a) to predict before stereotactic radiotherapy local tumor control, (b) to investigate temporal changes in tumor microcirculation after stereotactic radiotherapy, and (c) to analyze whether malignant glioma response may be predicted earlier by alterations in the tissue pharmacokinetics rather than in terms of tumor volume. Ninety MRI studies were performed of 18 patients with malignant glioma before and 6, 18, 26, 52, and 72 weeks after the end of stereotactic radiotherapy. The signal time courses of the contrast-enhanced tumors were analyzed using a pharmacokinetic two-compartment model that calculates for the parameter A, reflecting the degree of MRI signal enhancement [no units] and the exchange rate constant k21 [min(-1)]. Before radiotherapy, the amplitude A was significantly (P < .05) lower in patients with subsequent local tumor control (n = 8; mean A = .34 +/- .15) compared to patients without subsequent local tumor control (n = 10; mean A = .94 +/- .71). In the local tumor control group, early after stereotactic radiotherapy (at 6-18 weeks), there was a significant (P < .05) time-dependent decrease in the parameter k21, whereas there was still no alteration in the tumor volume. A low amplitude A before radiotherapy, combined with an early drop of k21 after stereotactic radiotherapy, reliably characterized the group of patients with subsequent tumor volume decrease. Our preliminary results suggest that two contrast-enhanced dynamic MR studies, one before and one early after stereotactic radiotherapy, offer important information on local tumor control within the first 6 to 18 weeks after stereotactic radiotherapy. Moreover, this response may be evidenced before tumor volume changes and provides a therapeutic window to broaden treatment options and to improve treatment outcome.

Brain↗

Fast fluid-attenuated inversion-recovery (FLAIR) MRI in the assessment of intraaxial brain tumors.

This study demonstrates the value of a fast fluid-attenuated inversion-recovery (FLAIR) technique in the assessment of primary intraaxial brain tumors. Twenty-one patients with primary intraaxial brain tumors were examined by T2-weighted, proton-density-weighted fast spin echo, fast FLAIR, and contrast-enhanced T1-weighted spin echo using identical slice parameters. The images were evaluated using quantitative and qualitative criteria. Quantitative criteria were tumor-to-background and tumor-to-cerebrospinal fluid (CSF) contrast and contrast-to-noise ratio (CNR). The qualitative evaluation was performed as a multireader analysis concerning lesion detection, lesion delineation, and image artifacts. In the qualitative evaluation, all readers found the fast FLAIR to be superior to fast spin echo in the exact delineation of intraaxial brain tumors (P < .001) and the delineation of enhancing and nonenhancing tumor parts. Fast FLAIR was superior in the delineation of cortically located and small lesions but was limited in lesions adjacent to the ventricles. Fast FLAIR provided a significantly better tumor-to-CSF contrast and tumor-to-CSF CNR (P < .001). The tumor-to-background contrast and tumor-to-background CNR of the fast FLAIR images were lower than those of T2-weighted spin-echo images but higher than those of proton-density-weighted spin-echo images. FLAIR images had more image artifacts influencing the image interpretation in only two patients. Signal hyperintensities at the ventricular border were present in 92% of the patients. They are common findings in fast FLAIR and should be included into the image interpretation.

Adult↗

Postoperative radiotherapy of astrocytomas.

Astrocytomas account for the majority of primary brain tumors. Low-grade tumors are slowly growing tumors with relatively long overall survival. However, a high percentage of these tumors transform to more malignant, high-grade tumors. High-grade gliomas (anaplastic astrocytomas and glioblastoma multiforme) have a poor prognosis. Treatment options are capable of prolonging the natural history of the disease, but the long-term survival is poor. This review discusses the different postoperative treatment options and the prognostic factors in low- and high-grade astrocytomas.

Adolescent↗

Adjuvant treatment of brain metastases.

With an incidence of 15/10(5) in the general population, brain metastases constitute a serious, debilitating complication in cancer patients. The majority of those patients suffer from more than one metastasis, but up to 30% to 40% present with a solitary lesion. Whole-brain radiotherapy (WBRT) extends median survival from 1 to 2 months for treatment with steroids only, to 4 to 6 months in most series. However, long-term survival (>1-2 years) is observed in up to 10% of patients with favorable prognostic factors, such as solitary lesions, good Karnofsky performance status, and absence of extracranial disease. For those patients, individually optimized treatment is worthwhile. For good-prognosis patients with controlled extracranial disease, surgery in combination with postoperative WBRT should be considered, especially when fast relief of symptoms is mandated. For surgically inaccessible solitary lesions below a size threshold of approximately 30 ccm, stereotactic radiosurgery (RS), although never compared to surgery in a randomized fashion, seems to yield comparable results and is the treatment of choice for more than one lesion in appropriately selected patients. Nevertheless, a number of questions concerning the optimal treatment regimens for brain metastases remain. These mainly concern the radiation dose, need for a combination of RS and WBRT, relative timing of different treatment modalities, and maximum number of brain metastases that can reasonably be treated with RS when long-term progression-free survival is the goal. However, RS is definitely an excellent option for salvage and palliation in patients with short life expectancy, as it is simultaneously noninvasive and cost-effective, with short hospitalization times.

Brain Neoplasms↗

Synthetic macromolecular drug carriers: biodistribution of poly[(N-2-hydroxypropyl)methacrylamide] copolymers and their accumulation in solid rat tumors.

To optimize polymer design for tumor directed drug delivery, the fate and the total body distribution of soluble synthetic macromolecules, derived from copolymers of [(N-2-(hydroxypropyl)methacrylamide] (HPMA) were monitored scintigraphically after radiolabeling with 131I during a seven day time window. Equimolar concentrations of radioiodinated copolymers of HPMA with small amounts of methacryloyltyrosinamide (pHPMA) differing in molecular weight (23.4 kD, 27.3 kD, 30.5 kD, 44 kD, 58.4 kD, 60.1 kD) were injected intravenously into Copenhagen rats bearing Dunning prostate carcinomas (subline R3327-AT1). Scintigraphic data were validated by determining absolute amounts of [131I]pHPMA in both tumor tissue and normal organs after sacrificing the animals. Copolymers were cleared from blood circulation in a molecular-weight dependent manner, either via excretion or by extravasation into normal and neoplastic tissues. While distribution patterns for pHPMAs in normal organs were quite similar, absolute amounts of copolymer uptake differed. The higher the molecular weight, the more radioactivity was taken up by the organs. Highest amounts of radioactivity were seen in the lung, liver, and spleen. In solid tumors, kinetics of pHPMA accumulation was clearly dependent on molecular weight. pHPMAs below the renal threshold peaked at 24 hours p.i. and then remained constant. In contrast, copolymers above the renal clearance threshold displayed a continuous accumulation reaching a significantly higher tumor uptake, presumably due to the very small or non existent polymer release from tumor tissue. Absolute amounts of tumor uptake determined by dissection analysis were 0.5 +/- 0.1% of injected dose/g tissue for the 27.3 kD pHPMA and 1.2 +/- 0.1% for the 60.1 kD pHPMA, respectively. In conclusion, our results demonstrate the influence of the molecular weight of the synthetic polymer pHPMA on plasma circulation time, excretion and organ clearance. While pHPMAs are cleared from all normal tissues except the spleen quite effectively, these polymers accumulate in solid tumors in a size dependent manner, due to the well known "enhanced permeability and retention" (EPR) effect. These data are of fundamental interest for ongoing studies on the pharmacokinetics of synthetic polymers, especially when these molecules are conjugated with targeting moieties and therapeutic or diagnostic agents.

Adenocarcinoma↗