Roee S. Lazebnik

Three-dimensional method for comparing in vivo interventional MR images of thermally ablated tissue with tissue response.

To investigate the ability of magnetic resonance (MR) to monitor radio‐frequency (RF) ablation treatments by comparing MR images of thermal lesions to histologically assayed cellular damage. We developed a new methodology using three‐dimensional registration for making spatial correlations.

Radiofrequency thermal ablation: correlation of hyperacute MR lesion images with tissue response.

To investigate the hypothesis that the outer boundary of the hyperintense region observed in hyperacute (several minutes post‐ablation) T2 and gadolinium contrast‐enhanced (CE) T1‐weighted magnetic resonance (MR) lesion images is an accurate predictor of eventual cell death from radiofrequency (RF) thermal ablation.

Three-Dimensional Registration of Magnetic Resonance Image Data to Histological Sections with Model-Based Evaluation

We developed a three-dimensional (3D) registration method to align medical scanner data with histological sections. After acquiring 3D medical scanner images, we sliced and photographed the tissue using, a custom apparatus, to obtain a volume of tissue section images. Histological samples from the sections were digitized using a video microscopy system. We aligned the histology and medical images to the reference tissue images using our 3D registration method. We applied the method to correlate in vivo magnetic resonance (MR) and histological measurements for radio-frequency thermal ablation lesions in rabbit thighs. For registration evaluation, we used an ellipsoid model to describe the lesion surfaces. The model surface closely fit the inner (M1) and outer (M2) boundaries of the hyperintense region in MR lesion images, and the boundary of necrosis (H1) in registered histology images. We used the distance between the model surfaces to indicate the 3D registration error. For four experiments, we measured a registration accuracy of 0.96± 0.13 mm (mean±SD) from the absolute distance between the M2 and H1 model surfaces, which compares favorably to the 0.70 mm in-plane MR voxel dimension. This suggests that our registration method provides sufficient spatial correspondence to correlate 3D medical scanner and histology data.

Volume registration using needle paths and point landmarks for evaluation of interventional MRI treatments

We created a method for three-dimensional (3-D) registration of medical images (e.g., magnetic resonance imaging (MRI) or computed tomography) to images of physical tissue sections or to other medical images and evaluated its accuracy. Our method proved valuable for evaluation of animal model experiments on interventional-MRI guided thermal ablation and on a new localized drug delivery system. The method computes an optimum set of rigid body registration parameters by minimization of the Euclidean distances between automatically chosen correspondence points, along manually selected fiducial needle paths, and optional point landmarks, using the iterative closest point algorithm. For numerically simulated experiments, using two needle paths over a range of needle orientations, mean voxel displacement errors depended mostly on needle localization error when the angle between needles was at least 20/spl deg/. For parameters typical of our in vivo experiments, the mean voxel displacement error was <0.35 mm. In addition, we determined that the distance objective function was a useful diagnostic for predicting registration quality. To evaluate the registration quality of physical specimens, we computed the misregistration for a needle not considered during the optimization procedure. We registered an ex vivo sheep brain MR volume with another MR volume and tissue section photographs, using various combinations of needle and point landmarks. Mean registration error was always /spl les/0.54 mm for MR-to-MR registrations and /spl les/0.52 mm for MR to tissue section registrations. We also applied the method to correlate MR volumes of radio-frequency induced thermal ablation lesions with actual tissue destruction. In this case, in vivo rabbit thigh volumes were registered to photographs of ex vivo tissue sections using two needle paths. Mean registration errors were between 0.7 and 1.36 mm over all rabbits, the largest error less than two MR voxel widths. We conclude that our method provides sufficient spatial correspondence to facilitate comparison of 3-D image data with data from gross pathology tissue sections and histology.

Automatic model-based evaluation of magnetic resonance-guided radio frequency ablation lesions with histological correlation

To develop a model‐based method for automatic evaluation of radio frequency (RF) ablation treatment using magnetic resonance (MR) images.

Sub-acute changes in lesion conspicuity and geometry following MR-guided radiofrequency ablation

To evaluate MR signal and lesion zone volume evolution through the sub‐acute phase following image‐guided radiofrequency (RF) thermal ablation.

Radio‐frequency‐induced thermal lesions: Subacute magnetic resonance appearance and histological correlation

To investigate the relationship between subacute magnetic resonance (MR) images of radio‐frequency (RF) ablation lesions and tissue viability as determined from histological tissue samples.

X-ray computed tomography methods for in vivo evaluation of local drug release systems

Recent advances in drug delivery techniques have necessitated the development of tools for in vivo monitoring of drug distributions. Gamma emission imaging and magnetic resonance imaging suffer from problems of resolution and sensitivity, respectively. We propose that the combination of X-ray CT imaging and image analysis techniques provides an excellent method for the evaluation of the transport of platinum-containing drugs from a localized, controlled release source. We correlated local carboplatin concentration with CT intensity, producing a linear relationship with a sensitivity of 62.6 /spl mu/g/mL per Hounsfield unit. As an example application, we evaluated the differences in drug transport properties between normal and ablated rabbit liver from implanted polymer millirods. The use of three-dimensional visualization provided a method of evaluating the placement of the drug delivery device in relation to the surrounding anatomy, and registration and reformatting allowed the accurate comparison of the sequence of temporal CT volumes acquired over a period of 24 h. Taking averages over radial lines extending away from the center of the implanted millirods and integrating over clinically appropriate regions, yielded information about drug release from the millirod and transport in biological tissues. Comparing implants in normal and ablated tissues, we found that ablation prior to millirod implantation greatly decreased the loss of drug from the immediate area, resulting in a higher average dose to the surrounding tissue. This work shows that X-ray CT imaging is a useful technique for the in vivo evaluation of the pharmacokinetics of platinated agents.

Noninvasive monitoring of local drug release in a rabbit radiofrequency (RF) ablation model using X-ray computed tomography

In this study, X-ray computed tomography (CT) was utilized as a noninvasive method to directly examine local drug release kinetics in livers before and following radiofrequency thermal ablation. Iohexol, a CT contrast agent, was used as a drug-mimicking molecule. Release of iohexol in healthy and ablated rabbit livers over 48 h was quantified and correlated with the release profiles from phosphate-buffered saline (PBS) in vitro. The results show that iohexol release in ablated livers is significantly slower than both release in normal livers and in vitro. The time at which 50% of the drug was released (t(1/2)) into ablated liver (20.6+/-5.9 h) was 1.7 times longer than in normal liver (12.1+/-5.4 h) and approximately two times longer than that in PBS (10.1+/-1.2 h). The slower release in ablated livers is a result of severe tissue damage inflicted by thermal ablation, as supported by histological examination. This data suggests that a noninvasive imaging method provides a superior measurement over in vitro release studies in accurately quantifying the local release kinetics of an agent in an altered physiological system in vivo. Because the development of a successful local drug therapy is dependent on the understanding of the agent release kinetics at the implantation site, the noninvasive data may be indispensable in effectively predicting the implant behavior in a physiological system.

Three-dimensional correlation of MR images to muscle tissue response for interventional MRI thermal ablation

We are treating tumors using radiofrequency (RF) ablation under interventional MRI (iMRI) guidance. We investigated the ability of MR to monitor the treated region by comparing MR thermal lesion images to cellular damage as seen histologically. Our new methodology allows 3D registration that should enable more accurate correlation than previous 2D methods. Using a low-field (0.2T) open magnet iMRI system for probe guidance, we applied RF ablation to the thigh muscle of four New Zealand White rabbits. To relate in vivo MR and histology images, we obtained intermediate ex vivo MR images and pictures of thick tissue slices obtained using a specially designed apparatus. Registration was done with a computer algorithm that matches tracks of needle fiducials placed near the tissue of interest. After registration, we determined the region inside the circular, hyperintense rim in MR closely corresponds to the region of necrosis as determined by histology on animals sacrificed 30 minutes after ablation. This is good evidence that iMRI images can be used for real-time feedback during thermal RF ablation treatments.