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R M Henkelman

Publications and source records attributed to R M Henkelman.

At least 19 recordsLinked to original sources
PubMed2006

Development of a high resolution three-dimensional surgical atlas of the murine head for strains 129S1/SvImJ and C57Bl/6J using magnetic resonance imaging and micro-computed tomography.

The mouse has emerged as a major experimental model system for examining the functional properties of the mammalian CNS; both during development and following CNS injury. Histologic procedures currently used to determine the relative position of structures within the CNS are presently limited in their ability to take full advantage of this system for surgical and morphometric procedures. We present here the first three-dimensional interactive digital atlas of the murine brain and skull for two genetically important strains of mice; 129S1/SvImJ and C57Bl/6J. The final resolution of these digital atlases is 54 micro m(3). These representations of the murine brain and skull, in conjunction with our development of a new, more dynamic master coordinate system, provide improved accuracy with respect to targeting CNS structures during surgery compared with previous systems. The interactive three-dimensional nature of these atlases also provide users with stereotactic information necessary to perform accurate "off-axis" surgical procedures, as is commonly required for experiments such as in vivo micro-electroporation. In addition, three-dimensional analysis of the brain and skull shape in C57Bl, 129Sv, CD1, and additional murine strains, suggests that a stereotactic coordinate system based upon the lambda and rostral confluence of the sinuses at the sagittal midline, provides improved accuracy compared with the traditional lambda-bregma landmark system. These findings demonstrate the utility of developing highly accurate and robust three-dimensional representations of the murine brain and skull, in which experimental outputs can be directly compared using a unified coordinate system. The aim of these studies is to enhance comparative morphometric analyses and stereotactic surgical procedures in mice.

Animals↗
PubMed2006

Comparing microsphere deposition and flow modeling in 3D vascular trees.

Blood perfusion in organs has been shown to be heterogeneous in a number of cases. At the same time, a number of models of vascular structure and flow have been proposed that also generate heterogeneous perfusion. Although a relationship between local perfusion and vascular structure has to exist, no model has yet been validated as an accurate description of this relationship. A study of perfusion and three-dimensional (3D) arterial structure in individual rat kidneys is presented, which allows comparison between local measurements of perfusion and model-based predictions. High-resolution computed tomography is used to obtain images of both deposited microspheres and of an arterial cast in the same organ. Microsphere deposition is used as an estimate of local perfusion. A 3D cylindrical pipe model of the arterial tree is generated based on an image of the arterial cast. Results of a flow model are compared with local microsphere deposition. High correlation (r(2) > 0.94) was observed between measured and modeled flows through the vascular tree segments. However, the relative dispersion of the microsphere perfusion measurement was two- to threefold higher than perfusion heterogeneity calculated in the flow model. Also, there was no correlation in the residual deviations between the methods. This study illustrates the importance of comparing models of local perfusion with in vivo measurements of perfusion in the same biologically realistic vascular tree.

Animals↗
PubMed2005

Estimating perfusion using microCT to locate microspheres.

The injection of microspheres into the blood stream has been a common method to measure the spatial distribution of blood flow (perfusion). A technique to conduct this kind of measurement in small animal organs is presented using silver-coated microspheres with a diameter of 16 microm and high-resolution computed tomography (microCT) to detect individual microspheres. Phantom experiments demonstrate the detectability of individual spheres. The distribution of microspheres within a rat heart is given as an example. Using non-destructive, three-dimensional imaging for microsphere detection avoids the cumbersome dissection of the organ into samples or slices and their subsequent registration. The detection of individual spheres allows high-resolution measurements of perfusion and arbitrary definition of regions of interest. These, in turn, allow for accurate statistical analysis of perfusion such as relative dispersion curves.

Animals↗
PubMed2004

A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability.

Although there is growing interest in finding mouse models of human disease, no technique for quickly and quantitatively determining anatomical mutants currently exists. Magnetic resonance imaging (MRI) is ideally suited to probe fine structures in mice. This technology is three-dimensional, non-destructive and rapid compared to histopathology; hence MRI scientists have been able to create detailed three-dimensional images of 60 mum resolution or better. The data is digital which lends itself to sophisticated image processing algorithms. Here we show a variational MRI atlas constructed from nine excised brains of 8 week old 129S1/SvImJ male mice. This new type of atlas is comprised of an unbiased average brain--created from alignment of the individual brains--and the mathematical descriptors of anatomical variation across the individuals. We found that the majority of internal points in the individuals never varied more than 117 microm from equivalent points in the atlas. A three-dimensional annotation of the average image was performed and used to estimate the mean and standard deviation of volumes in a variety of structures across the individual brains; these volumes never differed by more than 5%. Our results indicate that variational atlases of inbred strains represent a well-defined basis against which mutant outliers can be readily compared.

Algorithms↗
PubMed2003

Branching tree model with fractal vascular resistance explains fractal perfusion heterogeneity.

Perfusion heterogeneities in organs such as the heart obey a power law as a function of scale, a behavior termed "fractal." An explanation of why vascular systems produce such a specific perfusion pattern is still lacking. An intuitive branching tree model is presented that reveals how this behavior can be generated as a consequence of scale-independent branching asymmetry and fractal vessel resistance. Comparison of computer simulations to experimental data from the sheep heart shows that the values of the two free model parameters are realistic. Branching asymmetry within the model is defined by the relative tissue volume being fed by each branch. Vessel ordering for fractal analysis of morphology based on fed or drained tissue volumes is preferable to the commonly used Strahler system, which is shown to depend on branching asymmetry. Recently, noninvasive imaging techniques such as PET and MRI have been used to measure perfusion heterogeneity. The model allows a physiological interpretation of the measured fractal parameters, which could in turn be used to characterize vascular morphology and function.

Animals↗
PubMed2002

Can MTR be used to assess cartilage in the presence of Gd-DTPA2-?

Magnetization transfer (MT) and T(1) and T(2) relaxation of normal, trypsinized, and interleukin-1beta (IL-1beta)-treated cartilage were measured in the absence and presence of Gd-DTPA(2-). Without the addition of Gd-DTPA(2-), neither T(1) nor T(2) showed any significant change with cartilage damage. However, with Gd-DTPA(2-), trypsinized cartilage exhibited substantially shorter T(1) than normal cartilage, as expected due to the glycosaminoglycan (GAG) loss in these samples, and associated increased Gd-DTPA(2-) concentration. The T(2) results were similar, but less dramatic. The MT pseudo first-order exchange rate, RM(0B), did not depend on the contrast agent concentration, as expected, and was significantly faster for trypsinized and slower for IL-1beta-treated cartilage. In both cases, the MT fraction of the macromolecular pool M(0B) decreased while only trypsinized cartilage showed an increase in MT exchange rate R. The MT ratio (MTR) decreased with increasing Gd-DTPA(2-) concentration. However, interpretation of the MTR results in the presence of Gd-DTPA(2-) was complicated due to competing effects of increased longitudinal relaxivity and MT exchange. Therefore, in a cartilage sample with an unknown degree of GAG depletion and some collagen damage, a full MT analysis might be used to probe the molecular state of cartilage, but it would not be possible to use a simple MTR measurement after the administration of Gd-DTPA(2-) to differentially determine the amount of cartilage degradation in the sample.

Animals↗
PubMed2001

MR properties of rat sciatic nerve following trauma.

T(1) and T(2) relaxation times, magnetization transfer (MT), and diffusion anisotropy of rat sciatic nerve were measured at different time intervals following trauma. The nerve injury was induced by either cutting (irreversible nerve degeneration) or crushing (degeneration followed by regeneration). The MR properties were measured for proximal and distal portions of the injured nerve. The portions of the nerve proximal to the induced injury exhibited MR characteristics similar to those of normal nerves, whereas the distal portions showed significant differences in all MR parameters. These differences diminished in the regenerating nerves within approximately 4 weeks post injury. In the case of irreversible nerve damage, the differences in the distal nerves were slightly larger and did not resolve even 6 weeks after induced trauma. The MR measurements were correlated with histopathology exams. Observed changes in tissue microstructure, such as demyelination, inflammation, and axonal loss, can result in a significant increase in the average T(1) and T(2) relaxation times, reduction in the MT effect, and decrease in diffusion anisotropy. MR parameters, therefore, are very good indicators of nerve damage and may be useful in monitoring therapies that assist nerve regeneration. Magn Reson Med 45:415-420, 2001.

Animals↗
PubMed2001

Magnetization transfer in MRI: a review.

This review describes magnetization transfer (MT) contrast in magnetic resonance imaging. A qualitative description of how MT works is provided along with experimental evidence that leads to a quantitative model for MT in tissues. The implementation of MT saturation in imaging sequences and the interpretation of the MT-induced signal change in terms of exchange processes and direct effects are presented. Finally, highlights of clinical uses of MT are outlined and future directions for investigation proposed.

Biophysical Phenomena↗
PubMed2000

Proton-resonance frequency shift MR thermometry is affected by changes in the electrical conductivity of tissue.

The proton-resonance frequency (PRF) shift method of MR thermometry provides an easy and practical means of quantitatively monitoring in vivo temperatures for MR image-guided thermal-coagulation therapy. However, reported discrepancies in the numerical value of the PRF-thermal coefficient persist, when measured in a variety of experimental conditions and in different tissue types, both ex vivo and in vivo. In this report, a potential source of variation in the PRF-shift method of thermometry is identified that manifests as a constant incremental phase shift per unit change in temperature that is independent of the echo-time setting, when constructing temperature-sensitive phase images from a gradient-echo pulse sequence. It is proposed that this confounding phase-shift offset arises from thermally induced changes in the electrical conductivity of the material. To this end, it is demonstrated that the MR-derived temperature changes could be in error by as much as 28%, as measured from a simple calibration experiment on freshly excised cow liver. A simple method of overcoming this phase-shift offset is described.

Animals↗
PubMed2000

Gd-DTPA relaxivity depends on macromolecular content.

Gd-DTPA T(1) relaxivity of water protons was measured at 1.5 T and room temperature as a function of macromolecular content in model systems. Gd-DTPA relaxivity was found to increase with macromolecular concentration. The results of this study indicate that the Gd-DTPA relaxivity in tissue extracellular compartment could be as much as 30-70% higher than that of Gd-DTPA in saline. Quantitative MR analyses that use T(1) as an estimation of local Gd-DTPA concentration require a priori determination of the Gd relaxivity in tissue.

Animals↗
PubMed2000

Magnetic resonance thermometry for predicting thermal damage: an application of interstitial laser coagulation in an in vivo canine prostate model.

Magnetic resonance image-guidance for interstitial thermal therapy has proven to be a valuable tool in its traditional role in device localization and, more recently, in monitoring heat deposition within tissue. However, a quantitative understanding of how temperature-time exposure relates to thermal damage is crucial if the predictive value of real-time MR thermal-monitoring is to be fully realized. Results are presented on interstitial laser coagulation of two canine prostate models which are shown to provide an opportunity to evaluate three models of thermal damage based on a threshold maximum temperature, an Arrhenius damage integral, and a temperature-time product. These models were compared to the resultant lesion margin as derived from post-treatment T(1)- and T(2)-weighted MR images, as well as from direct histological evaluation of the excised canine prostate. Histological evaluation shows that the thermal-injury boundary can be predicted from a threshold-maximum temperature of approximately 51 degrees C or an equivalent Arrhenius t(43) period of 200 minutes, but it is not reliably predicted using the temperature-time product. The methods described in this study are expected to have implications for the treatment of benign prostatic hyperplasia and prostate cancer with interstitial laser coagulation, which will be the focus of future human studies.

Animals↗
PubMed2000

Comparison of thermal damage calculated using magnetic resonance thermometry, with magnetic resonance imaging post-treatment and histology, after interstitial microwave thermal therapy of rabbit brain.

Clinical application of high-temperature thermal therapy as a treatment for solid tumours requires an accurate and close to real-time method for assessing tissue damage. Imaging methods that detect structural changes during heating may underestimate the extent of thermal damage. This is due to the occurrence of delayed damage manifested at tissue locations exposed to temperatures lower than those required to cause immediate structural changes. An alternative approach is to measure temperature and then calculate the expected damage based on the temperature history at each tissue location. Magnetic resonance (MR) imaging methods now allow temperature maps of the target and surrounding tissues to be generated in almost real-time. The aim of this work was to evaluate whether thermal damage zones calculated on the basis of MR thermometry maps measured during heating correspond to actual tissue damage as measured after treatment by histological methods and MR imaging. Four male rabbits were treated with high-temperature thermal therapy delivered in the brain by a single microwave antenna operating at 915 MHz. MR scanning was performed before, during and after treatment in a 1.5 T whole-body scanner. Temperature maps were produced using the proton resonance frequency (PRF) shift method of MR thermometry. In addition, conventional T1-weighted and T2-weighted spin-echo images were acquired after treatment. Thermal damage zones corresponding to cell death, microvascular blood flow stasis and protein coagulation were calculated using an Arrhenius analysis of the MR temperature/time course data. The calculated zones were compared with the lesions seen on histopathological examination of the brains which were removed within 6-8 h of treatment. The results showed that calculated damage zones based on MR thermometry agreed well with areas of damage as assessed using histology after heating was completed. The data suggest that real-time calculations of final expected thermal damage based on an Arrhenius analysis of MR temperature data may provide a useful method of real-time monitoring of thermal therapy when combined with conventional T2-weighted images taken after treatment.

Animals↗
PubMed2000

Prostate cancer: MR imaging and thermometry during microwave thermal ablation-initial experience.

Percutaneous interstitial microwave thermoablation of locally recurrent prostate carcinoma was continually guided with magnetic resonance (MR) imaging. Phase images and data were obtained with a rapid gradient-echo technique and were used to derive tissue temperature change on the basis of proton-resonance shift. Thermally devitalized regions correlated well with the phase image findings. MR imaging-derived temperatures were linearly related to the fluoroptic tissue temperatures. MR imaging can be used to guide thermoablation.

Aged↗
PubMed1999

Quantifying tissue damage due to focused ultrasound heating observed by MRI.

Focused ultrasound heating of ex vivo bovine kidney and liver was monitored using magnetic resonance imaging (MRI) to investigate the quantitative relationship between time-dependent temperature elevations and altered contrast in MR images due to thermal coagulation. Proton resonance frequency shift MR thermometry was performed during heating at 10 sec intervals (single-slice fast spoiled GRASS [FSPGR], theta/TE/TR 30 degrees/11/39 msec, field of view 8 cm, 256 x 256, 3 mm slice thickness, 1 NEX); post-heating MR images were T1-weighted (3D-FSPGR, theta/TE/TR 60 degrees/25/200 msec, 1 mm slice thickness, 3 NEX). Analysis of the resulting temperature versus time data using the Arrhenius relationship and a simple binary discrimination model showed that thermal coagulation occurred with heating at approximately 54 degrees C for 10 sec in both tissues and could be predicted with approximately 625 microm spatial resolution. These results suggest that quantitative MR guidance of thermal coagulation therapy is feasible, and they provide information useful for designing future investigations in vivo.

Animals↗
PubMed1999

Heat-source orientation and geometry dependence in proton-resonance frequency shift magnetic resonance thermometry.

The proton-resonance frequency (PRF) shift method of thermometry has become a promising tool for magnetic resonance image-guided thermal therapies. Although the PRF thermal coefficient has recently been shown to be independent of tissue type when measured ex vivo, significant discrepancy remains on its value for tissues measured in vivo under a variety of experimental conditions. The authors identify a potential source of variation in the PRF thermal coefficient that arises from temperature-induced changes in the volume magnetic susceptibility of tissue and is dependent on the orientation and geometry of the heat-delivery device and its associated heat pattern. This study demonstrates that spatial variations in the apparent PRF thermal coefficient could lead to errors of up to +/-30% in the magnetic resonance estimated temperature change if this effect is ignored.

Algorithms↗
PubMed1999

Analysis of changes in MR properties of tissues after heat treatment.

To characterize changes in the MR parameters of tissues due to thermal coagulation, a series of T(1), T(2), diffusion, and magnetization transfer measurements were performed on a variety of ex vivo tissues: murine slow twitch skeletal muscle, murine cardiac muscle, murine cerebral hemisphere, bovine white matter, murine liver tissue, bovine retroperitoneal adipose tissue, hen egg white, human prostate and human blood. Standardized heat treatments were performed for each tissue type, over the temperature range from 37 degrees C to 90 degrees C. For all tissues, changes in each MR measurement resulting from thermal coagulation were observed above a threshold temperature of approximately 60 degrees C. These changes are explained based on biophysical knowledge of thermal damage mechanisms and the MR properties of normal tissues, and are particularly relevant for interpreting the changes in image contrast that are observed when MRI is used to guide and monitor thermal coagulation therapy procedures. Magn Reson Med 42:1061-1071, 1999.

Adipose Tissue↗
PubMed1999

Characterizing white matter with magnetization transfer and T(2).

A magnetization-transfer (MT) CPMG hybrid experiment was performed to analyze T(2) relaxation and MT characteristics in bovine optic nerve. Two exchanging liquid pools with their own, independent MT characteristics were necessary to model both the T(2) relaxation and the MT data. The model agrees well with the experimental data and yields physically realistic parameters. The MT effect for myelin water is approximately nine time larger than that for intra/intercellular water, indicating that the MT characteristics observed for white matter are mainly related to myelin. The model can be used to probe parameters that would be difficult to achieve experimentally. The exchange process between the two tissue compartments does not drastically affect the amplitudes and relaxation rates of the T(2) components, but is fast enough to significantly influence their MT characteristics. Although, both the MT and T(2) experiments described in this paper are too time consuming to be applied in routine clinical work, presented results can be useful in interpreting clinical pulse sequences that are sensitive to myelin. Magn Reson Med 42:1128-1136, 1999.

Animals↗