Walter J. Lorenz

Pharmacokinetic Parameters in Cns Gd-dtpa Enhanced Mr Imaging

Dynamic MR imaging can be used to study tissue perfusion and vascular permeability. In the present article a procedure for dynamic MR is presented, which (a) accurately resolves the fast kinetics of tissue response during and after intravenous infusion of the paramagnetic contrast medium Gd-DTPA and (b) yields a linear relationship between the measured MR signal and the Gd-DTPA concentration in the tissue. According to these features, the measured signal-time curves can be analyzed within the framework of pharmacokinetic modeling. Tissue response has been parameterized using a linear two-compartment open model, with only negligible effects of the peripheral compartment on the central compartment. The three model parameters were fitted to the signal-time data pixel by pixel, based on a set of 64 rapid SE images (SE 100/10 ms, image scan time 13 s, interscan intervals 11 s). This makes it possible to construct parameter images, whereby structures become visible that cannot be distinguished in conventional Gd-DTPA enhanced MR. As a clinical example, the approach is discussed in a case of glioblastoma.

Cerebral radiation surgery using moving field irradiation at a linear accelerator facility.

A modified irradiation technique at a linear accelerator facility for radiation surgery within the brain is described consisting of several moving field irradiations in non-coplanar planes. Using collimated narrow beams, a localization system and special computer programs for precise patient positioning, a high concentration of dose within small, well circumscribed volumes is obtained. Resulting dose distributions were studied experimentally and by calculations. A simple algorithm for treatment planning was developed and based on CT images. Radiation surgery within the brain is now technically feasible at our linear accelerator. Seventeen patients have now been treated.

Stereotactic percutaneous single dose irradiation of brain metastases with a linear accelerator

The effectivity of stereotactic percutaneous single dose irradiations in the treatment of solitary brain metastases has been assessed in a series of 12 consecutive patients. Only radioresistant deeply localized metastases have been treated. Photon-irradiation was carried out with the convergent beam technique using stereotactic localization methods, in a linear accelerator facility. In 11 of the 12 patients no side effects occurred. The first 7 patients, who could be observed 3 months or longer, have been studied in detail. In each of these cases single dose irradiation with 20-30 Gy yielded arrest of tumor growth. In one case a marked decrease in contrast enhancement and in four cases shrinkage of the metastasis as well as a marked decrease of the edema occurred. In every patient a marked, sometimes dramatic improvement of the clinical condition was achieved, beginning a few days after irradiation. Stereotactic radiosurgery is a valuable tool in the treatment of inoperable, radioresistant brain metastases, the major advantage being high efficacy and smoothness of the procedure, as well as extremely short hospitalization times (2-3 days).

Three dimensional image correlation of CT, MR, and PET studies in radiotherapy treatment planning of brain tumors

Abstract A treatment planning system for stereotactic convergent beam irradiation of deeply localized brain tumors is reported. The treatment technique consists of several moving field irradiations in noncoplanar planes at a linear accelerator facility. Using collimated narrow beams, a high concentration of dose within small volumes with a dose gradient of 10-15%/mm was obtained. The dose calculation was based on geometrical information of multiplanar CT or magnetic resonance (MR) imaging data. The patients head was fixed in a stereotactic localization system, which is usable at CT, MR, and positron emission tomography (PET) installations. Special computer programs for correction of the geometrical MR distortions allowed a precise correlation of the different imaging modalities. The therapist can use combinations of CT, MR, and PET data for defining target volume. For instance, the superior soft tissue contrast of MR coupled with the metabolic features of PET may be a useful addition in the radiation treatment planning process. Furthermore, other features such as calculated dose distribution to critical structures can also be transferred from one set of imaging data to another and can be displayed as three-dimensional shaded structures.

Fast and precise T1 imaging using a TOMROP sequence

Proton spin-lattice (T1) relaxation time images were computed from a data set of 32 gradient-echo images acquired with a fast TOMROP (T One by Multiple Read Out Pulses) sequence using a standard whole-body MR imager operating at 64 MHz. The data acquisition and analysis method which permits accurate pixel-by-pixel estimation of T1 relaxation times is described. As an example, the T1 parameter image of a human brain is shown demonstrating an excellent image quality. For white and gray brain matter, the measured longitudinal relaxation processes are adequately described by a single-component least-squares fit, while more than one proton component has to be considered for fatty tissue. A quantitative analysis yielded T1 values of 547 +/- 36 msec and 944 +/- 73 msec for white and gray matter, respectively.

Computer systems and mechanical tools for stereotactically guided conformation therapy with linear accelerators

An integrated system for fractionated, stereotactically guided conformation radiotherapy has been developed. The system components are a stereotactic fixation system that can be used each treatment day, a localization, and positioning unit that can be used during x-ray computer tomography, magnetic resonance imaging, positron emission tomography, and radiographical examinations as well as for treatment. Conformal precision radiotherapy is planned with a new three-dimensional treatment planning system (Voxel-Plan-Heidelberg) which comprises, among others options, a three-dimensional image correlation procedure as well as routines for the calculation of coplanar and non-coplanar irradiations with irregularly shaped fields. Two different multi-leaf collimators have been designed for precision radiotherapy in the head and neck region. A manual multi-leaf collimator is used for irradiations with stationary beams or for moving beam treatments with invariable irregularly shaped fields. This collimator system is now being used for patient treatments. The design of a computer controlled multi-leaf collimator unit for multiple fixed field irradiation techniques is discussed. All system components are aimed at conforming dose distributions for fractionated radiotherapy treatments to the target to improve sparing of adjacent normal tissues, and at achieving a sufficient geometrical accuracy in the dose application.

The role of high-dose, single-fraction irradiation in small and large intracranial arteriovenous malformations

PURPOSE Radiosurgery with external beam irradiation is an accepted treatment for small intracranial vascular malformations. It has been proven effective and safe for lesions with volumes of less than 4 cc. However, there is only some limited clinical data for malformations of grade 4 and grade 5, according to Spetzler and Martin. METHODS AND MATERIALS At the Heidelberg radiosurgery facility equipped with a linear accelerator, 212 patients with cerebral arteriovenous malformations have been treated since 1984. Thirty-eight percent of the arteriovenous malformations treated were classified inoperable, 14% grade 5, 19% grade 4, and 29% grades 1-3. Radiation doses between 10 and 29 Gy were applied to the 80% isodose contour. RESULTS Above a threshold dose of 18 Gy, the overall obliteration rate was 72%. After 3 years, the obliteration rates were 83% with volumes of less than 4.2 cc, 75% with volumes of up to 33.5 cc, and 50% with volumes of up to 113 cc. Of the patients presenting with seizures and paresis, 83% and 56%, respectively, showed improvement, which correlated with the degree of obliteration. After a follow-up period of up to 9 years, the rate of radiation-induced severe late complications was 4.3%. In grade 5 lesions, the risk of side effects was 10%. No serious complications occurred if a maximum dose of less than 25 Gy was applied to treatment volumes of less than 33.5 cc. CONCLUSION The success of stereotactic high-dose irradiation of arteriovenous malformations depends on the dose applied. The incidence of radiation-induced side effects increased with the applied dose and treatment volumes. From our experience, doses of less than 25 Gy and treatment volumes of up to 33.5 cc are safe and effective. In the future, new techniques of radiosurgery with linear accelerators and dynamically reshaped beams will allow us to apply homogenous dose distributions. Additional use of magnetic resonance angiography for 3D treatment planning will help to identify the nidus more easily.

MR imaging of fat-containing tissues : valuation of two quantitative imaging techniques in comparison with localized proton spectroscopy

Since lipid protons, consisting mainly of triacylglycerols (TAG), are rather mobile, magnetic resonance imaging (MRI) is ideally suited for the examination of fat-containing tissues such as bone marrow. In contrast to water protons, however, lipid protons are chemically distinct and give rise to at least eight resonance peaks with different T1 and T2 relaxation times in the 1H spectrum. This is why the characterization of fat-containing tissues by quantitative MRI is much more difficult than that of most other tissues. In our study we wanted to examine the accuracy and the potential of a 1H chemical shift imaging (CSI) technique and a multiple spin-echo imaging (MSEI) technique. A stimulated-echo (STEAM) sequence for spatially localized proton spectroscopy was used as the reference method. In the first part of this paper, we describe quantitative imaging experiments which were performed to assess the accuracy of the fat-water separation according to the Dixon method and the bi-exponential decomposition of the MSEI data. For that purpose, we used a two-compartment phantom filled with either an aqueous Gd-DTPA solution and vegetable oil or with two different aqueous Gd-DTPA solutions, respectively. The analysis of the 1H CSI data revealed that the presence of non-methylen protons in neutral fats leads to a slight under-estimation (of about 15%) of the relative fat fraction. The error is described theoretically and verified quantitatively by STEAM measurements. The bi-exponential analysis of the transverse relaxation data, on the other hand, yields reliable T2 values if the relative proton density of both components is higher than 15%. IN the second part of our investigation, the same techniques were applied to acquire data from the subcutaneous fatty tissue, the femoral head, and the lumbar vertebrae of three healthy volunteers. In the bone marrow spectra, only two broad resonances could be resolved; they were superpositions of diverse molecular groups with different T1 and T2 relaxation times. In these cases, localized proton spectroscopy does not provide additional information with respect to 1H CSI. The MSEI data of the three examined fat containing tissue regions were adequately fitted by a bi-exponential function despite the fact that there were much more chemically distinct protons present in fatty tissues.

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.

Multiexponential proton spin-spin relaxation in MR imaging of human brain tumors

In vivo measurements of proton relaxation processes in human brain tumors have been performed by magnetic resonance (MR) imaging using a whole-body superconductive MR scanner, operating at 1.5 T. The Tl and T2 relaxation time measurements were based on a combined Carr-Purcell/ Carr-Purcell-Meiboom-Gill sequence with two interleaved repetition times and 32 echoes. First, comparative measurements in the imager and with the spectrometer of relaxation times were performed on phantoms containing fluids of different Tl and T2 to evaluate accuracy. A maximum deviation of ∼10% was found. Multislicing with a gap width of one slice thickness influenced the accuracy of Tl relaxation measurement. A gap width of at least two times the slice thickness was necessary for reliable determination of Tl. No influence on T2 values was observed by multislicing. Second, in human head imaging the multiexponential behavior of the T2 decay curves has been analyzed in each pixel, where the mean square deviation has been used as a criterion to discriminate between mono- and biexponential behavior. Mean values of monoex-ponential Tl and multiexponential T2 relaxation data for white matter, gray matter, CSF, edema, and tumor were sampled in 12 patients with brain tumors. T2 showed monoexponential behavior in white and gray matter, whereas CSF, edema, and tumor showed distinct biexponentiality. The biexponential analysis generally yields “fast” and “slow” components with T2f = 80 ± 17 ms and T2S = 2,030 ± 210 ms for CSF (partial volume effect), T2f = 104 ± 25 ms and T2S = 677 ± 152 ms for edematous tissues, T2f = 97 ± 19 ms and T2S = 756 ± 99 ms for tumor tissues, respectively. Using a stepwise discriminant analysis by forward selection, the two best discriminating parameters of the multiexponential relaxation analysis for each pair of classification groups have been selected. For the discrimination of edematous and tumor tissues a retrospective overall accuracy of 94% has been found.