Semiautomatic parametric model-based 3D lesion segmentation for evaluation of MR-guided radiofrequency ablation therapy.

RATIONALE AND OBJECTIVES: Interventional magnetic resonance imaging (iMRI) allows real-time guidance and optimization of radiofrequency ablation of pathologic tissue. For many tissues, resulting lesions have a characteristic two-boundary appearance featuring an inner region and an outer hyper-intense margin in both T2 and contrast-enhanced (CE) T1-weighted MR images. We created a geometric model-based semiautomatic method to aid in real-time lesion segmentation, cross-sectional/three-dimensional visualization, and intra/posttreatment evaluation. MATERIALS AND METHODS: Our method relies on a 12-parameter, 3-dimensional, globally deformable model with quadric surfaces that describe both lesion boundaries. We present an energy minimization approach to quickly and semiautomatically fit the model to a gray-scale MR image volume. We applied the method to in vivo lesions (n = 10) in a rabbit thigh model, using T2 and CE T1-weighted MR images, and compared the results with manually segmented boundaries. RESULTS: For all lesions, the median error was < or =1.21 mm for the inner region and < or =1.00 mm for the outer hyper-intense region, values that favorably compare to a voxel width of 0.7 mm and distances between the borders manually segmented by the two operators. CONCLUSION: Our method provides a precise, semiautomatic approximation of lesion shape for ellipsoidal lesions. Further, the method has clinical applications in lesion visualization, volume estimation, and treatment evaluation.

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.

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

PURPOSE: 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. MATERIALS AND METHODS: A low-field, open MR imaging system was used to guide an ablation electrode into a thigh muscle of five rabbits and acquire in vivo T2 and CE T1-weighted MR volumes. Ablation occurred by applying RF current for two minutes with the electrode's temperature maintained at 90 degrees +/- 2 degrees C. After fixation, we sliced and photographed the tissue at 3 mm intervals, using a specially designed apparatus, to obtain a volume of tissue images. Digital images of hematoxylin and eosin (H&E) and Masson trichrome-stained histologic samples were obtained, and distinct regions of tissue damage were labeled using a video microscopy system. After the MR and histology images were aligned using a three-dimensional registration method, we compared tissue damage boundaries identified in histology with boundaries marked in MR images. RESULTS: The lesions have distinct zones of tissue damage histologically: a central zone of necrotic cells surrounded by an outer zone with cells that appeared non-viable and associated with marked interstitial edema. In 14 histology images from five lesions, the inner and outer boundaries of the outer zone were compared with the boundaries of a hyperintense rim that surrounds a central hypointense region in the T2 and CE T1-weighted MR images. For T2 and CE T1-weighted MR images, respectively, the mean absolute distance was 1.04 +/- 0.30 mm (mean +/- SD) and 1.00 +/- 0.34 mm for the inner boundaries, and 0.96 +/- 0.34 mm and 0.94 +/- 0.44 mm for the outer boundaries. The mean absolute distances for T2 and CE T1-weighted MR images were not sufficiently different to achieve statistical significance (P = 0.745, 0.818, for the inner and outer boundary, respectively). CONCLUSION: In hyperacute T2 and CE T1-weighted MR lesion images, observations strongly suggest that the outer boundary of the hyperintense rim corresponds to the region of eventual cell necrosis within a distance comparable to our ability to measure. This is good evidence that during RF ablation procedures, MR lesion images can be used to accurately localize the zone of irreversible tissue damage at the lesion margin.

The role of ultrasound in pregnancy-related emergencies.

Most complications of pregnancy allow time for transfer to specialized obstetric ultrasound units, but many women present to the emergency room or the labor and delivery unit with signs and symptoms suggesting genuine acute medical emergencies, where successful outcome depends on prompt diagnosis of the disorder and rapid appropriate medical management. The use of ultrasound technology in obstetric emergencies is well established. Ultrasonography plays a major role in such cases as the most important tool clinicians are using to identify the correct etiology and diagnosis, whereas in other cases it helps limit the differential diagnosis. One of the goals of any advanced training program in obstetrics and gynecology and radiology is to allow the skilled physician to perform the proper ultrasound study in case of an obstetric emergency to facilitate the proper diagnosis, enabling the medical team to provide the best possible care.

The prenatal presentation of congenital erythropoietic porphyria: report of two siblings with elevated maternal serum alpha-fetoprotein.

Congenital erythropoietic porphyria (CEP), also termed Günther's disease, is extremely rare and is inherited as an autosomal recessive trait. The mutation that causes the most severe deficiency of the enzyme uroporphyrinogen III synthase (URO-synthase) is C73R. Inheritance of two abnormal alleles results in the accumulation of porphyrins of isomer type I that are biologically useless but cause a wide spectrum of abnormalities in multiple organs. The intrauterine diagnosis of the first affected conceptus within a family is extremely challenging despite abnormal ultrasound findings suggesting severe fetal anemia. We report the abnormal findings in a pair of successive pregnancies in a single Caucasian family that yielded two C73R homozygous affected offspring. The course of the pregnancies, sonographic and laboratory abnormalities, method used for intrauterine diagnosis, therapeutic interventions, and variability of outcome between cases within a single family and the difficulty in managing even prenatally diagnosed cases are reported and discussed.

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

PURPOSE: To develop a model-based method for automatic evaluation of radio frequency (RF) ablation treatment using magnetic resonance (MR) images. MATERIALS AND METHODS: RF current lesions were generated in a rabbit thigh model using MR imaging (MRI) guidance. We created a 12-parameter, three-dimensional, globally deformable model with quadric surfaces that delineates lesion boundaries and is automatically fitted to MR grayscale data. We applied this method to in vivo T2- and contrast-enhanced (CE) T1-weighted MR images acquired immediately post-ablation and four days later. We then compared results to manually segmented MR and three-dimensional registered corresponding histological boundaries of cellular damage. RESULTS: Resulting lesions featured a two-boundary appearance with an inner region and an outer hyperintense margin on MR images. For automated vs. manual MR boundaries, the mean errors over all specimens were 0.19 +/- 0.51 mm and 0.27 +/- 0.52 mm for the inner surface, and -0.29 +/- 0.40 mm and -0.12 +/- 0.17 mm for the outer surface, for T2- and CE T1-weighted images, respectively. For automated vs. histological boundaries, mean errors over all specimens were 0.07 +/- 0.64 mm and 0.33 +/- 0.71 mm for the inner surface, and -0.27 +/- 0.69 mm and 0.02 +/- 0.43 mm for the outer surface, for T2- and CE T1-weighted images, respectively. All boundary errors compared favorably to MR voxel dimensions, which were 0.7 mm in-plane and 3.0 mm thick. CONCLUSION: The method is accurate both in describing MR-apparent boundaries and in predicting histological response and has applications in lesion visualization, volume estimation, and treatment evaluation.

Three-dimensional comparison of interventional MR radiofrequency ablation images with tissue response.

OBJECTIVE: Solid tumors are being treated using radiofrequency (RF) ablation under interventional magnetic resonance imaging (MRI) guidance. We are investigating the ability of MRI to monitor ablation treatments by comparing MR images of thermal lesions to histologically assayed tissue damage. MATERIAL AND METHODS: An open MRI system was used to guide an ablation electrode into five rabbit thigh muscles and acquire post-ablation MR image volumes. We developed a methodology using a 3D computer registration to make spatial correlations. After MR and histology images were registered with an accuracy of 1.32+/-0.39 mm (mean+/-SD), a boundary of necrosis identified in the histology was compared with the outer boundary of the hyperintense region in MR images. RESULTS: For 14 T2-weighted MR images, the absolute distance between boundaries was 0.96+/-0.34 mm (mean+/-SD). Since the small discrepancy between boundaries is comparable to our registration accuracy, the boundaries may match exactly. Similar correlations to histology were obtained with a deformable model segmentation method. CONCLUSIONS: This is good evidence that MR thermal lesion images can be used during RF ablation treatments to accurately localize the zone of necrosis at the lesion margin.

Radio-frequency-induced thermal lesions: subacute magnetic resonance appearance and histological correlation.

PURPOSE: 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. MATERIALS AND METHODS: We generated lesions (N = 5) in a rabbit thigh model. Four days later, we obtained in vivo T(2)- and contrast-enhanced (CE) T(1)-weighted images and ex vivo histological samples approximately perpendicular to the electrode path. Using three-dimensional registration and warping, we spatially compared manually segmented boundaries apparent on MR images to boundaries separating distinct histological zones determined from hematoxylin and eosin (H&E) and Masson trichrome (MT) stains, as well as birefringence studies. RESULTS: Lesions have a characteristic MR appearance: an outer hyperintense margin (M2) separating background tissue (M3) from an inner core (M1), in both T(2) and CE T(1) images. Histologically, there are two zones of damage: an outer zone of likely nonviable cells (H2) separating background tissue (H3) from an inner core of coagulated nonviable cells (H1). We measured distances between automatically computed correspondence points along histological and MR boundaries. For T(2) and CE T(1) images, respectively, M1 vs. H1 distances were 0.72 +/- 0.99 mm (mean +/- SD) and 0.10 +/- 0.95 mm, while outer M2 vs. H2 boundary distances were 0.26 +/- 1.16 mm and 0.05 +/- 1.08 mm. The discrepancy between histological and MR boundaries was larger than the variability in segmenting MR images, but probably within registration error. There were no significant differences between T(2) and CE T(1) boundaries. CONCLUSION: Lesion boundaries apparent in both T(2)- and CE T(1)-weighted MR scans, performed several days postablation, similarly predict the histological response. That is, the lesion core (M1) corresponds to nonviable coagulated cells (H1), while the hyperintense margin (M2) corresponds to likely nonviable cells undergoing necrotic changes (H2).

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

PURPOSE: To evaluate MR signal and lesion zone volume evolution through the sub-acute phase following image-guided radiofrequency (RF) thermal ablation. MATERIALS AND METHODS: For many tissues, including muscle and liver, thermal lesions that result from RF heating have a characteristic two-boundary appearance featuring an inner core (zone I) surrounded by a hyper-intense margin (zone II) and normal tissue (zone III), found in both T(2) and contrast enhanced (CE) T(1)-weighted MR images, both immediately post-ablation and four days later. First, we compared corresponding points between manually segmented zone boundaries apparent in T(2)- and CE T(1)-weighted images. Second, we examined the contrast-to-noise ratio (CNR) between all zone combinations. Third, we quantified the volume of zone I, zone II, and the entire lesion using a three-dimensional lesion geometry model fitted to segmented images. RESULTS: On a slice-by-slice basis, no statistically significant differences were found between zone boundaries apparent in T(2) and CE T(1)-weighted images. The contrast to noise ratio (CNR) of zone I vs. zone II, zone I vs. background muscle, and zone II vs. background muscle was always equal or greater for T(2)-weighted images than for CE T(1)-weighted images. In addition, by day four, zone II significantly increased in intensity compared to background muscle. The median Zone I volume increase was 44.2% (42.6%) using T(2) weighted images and 55.5% (68.7% interquartile range) using CE T(1)- weighted images. This expansion likely corresponds to an enlargement of the ablated, coagulative necrosis, region. The median Zone II volume increase was 15.0% (42.6%) using T(2)- weighted images 1.5% (38.8%) using CE T(1)-weighted images. CONCLUSIONS: 1) There are no significant differences between the apparent zone boundaries in T(2)- and CE T(1)-weighted images; 2) CNR is equal or greater for T(2)-weighted images as compared to CE T(1)-images; and 3) both the inner and outer lesion zone volumes typically increase several days post-ablation.

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 degrees. 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 < or = 0.54 mm for MR-to-MR registrations and < or = 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.

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

PURPOSE: 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. MATERIALS AND METHODS: A low-field, open MRI system was used to guide an ablation probe into rabbit thigh muscle and acquire MR volumes after ablation. After fixation, we sliced and photographed the tissue at 3-mm intervals, using a specially designed apparatus, to obtain a volume of tissue images. Histologic samples were digitized using a video microscopy system. For our three-dimensional registration method, we used the tissue images as the reference, and registered histology and MR images to them using two different computer alignment steps. First, the MR volume was aligned to the volume of tissue images by registering needle fiducials placed near the tissue of interest. Second, we registered the histology images with the tissue images using a two-dimensional warping technique that aligned internal features and the outside boundary of histology and tissue images. RESULTS: The MR and histology images were very well aligned, and registration accuracy, determined from displacement of needle fiducials, was 1.32 +/- 0.39 mm (mean +/- SD), which compared favorably to the MR voxel dimensions (0.70 mm in-plane and 3.0 mm thick). A preliminary comparison of MR and tissue response showed that the region inside the elliptical hyperintense rim in MR closely corresponds to the region of necrosis as established by histology, with a mean absolute distance between MR and histology boundaries of 1.17 mm, slightly smaller than the mean registration error. The MR region slightly overestimated the region of necrosis, with a mean signed distance between boundaries of 0.85 mm. CONCLUSION: Our results suggest that our methodology can be used to achieve three-dimensional registration of histology and in vivo MR images. In MR lesion images, the inner border of the hyperintense region corresponds to the border of irreversible cell damage. This is good evidence that during RF ablation treatments, iMRI lesion images can be used for real-time feedback.

Three-dimensional model of lesion geometry for evaluation of MR-guided thermal ablation therapy.

RATIONALE AND OBJECTIVES: High-radiofrequency energy is used clinically to ablate pathologic tissue with interventional magnetic resonance (MR) imaging. For many tissues, resulting lesions have a characteristic appearance on contrast-enhanced T1- and T2-weighted MR images, with two boundaries enclosing an inner hypointense region and an outer hyperintense margin. Geometric modeling of three-dimensional thermal lesions in animal experiments and patient treatments would improve analyses and visualization. MATERIALS AND METHODS: The authors created a model with two quadric surfaces and 12 parameters to describe both lesion surfaces. Parameters were estimated with iterative optimization to minimize the sum of the squared shortest distances from segmented points to the model surface. The authors validated the estimation process with digital lesion phantoms that simulated varying levels of segmentation error and missing surface information. They also applied their method to in vivo images of lesions in a rabbit model. RESULTS: For simulated phantom lesions, the lesion geometry was accurate despite manual segmentation error and incomplete surface data. Even when 50% of the surface was missing, the median error was less than 0.5 mm. For all in vivo lesions, the median distance from the model surface to data was no more than 0.58 mm for both inner and outer surfaces, less than a voxel width (0.7 mm). The interquartile range was 0.89 mm or less for all data. CONCLUSION: The authors' model provides a good approximation of actual lesion geometry and is highly resistant to missing segmentation information. It should prove useful for three-dimensional lesion visualization, volume estimation, automated segmentation, and volume registration.

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.

Clinical interpretation and recommendations for patients with a variant of uncertain significance in BRCA1 or BRCA2: a survey of genetic counseling practice.

The intent of this study was to document current practices in breast cancer genetic counseling and identify areas of variability for patients with a variant of uncertain significance (VUS) in the BRCA1 or BRCA2 gene. Registered members of the National Society of Genetic Counselors (NSGC) Cancer Special Interest Group (SIG) were sent an invitation via electronic mail to participate in an online questionnaire. The questionnaire was divided into three sections: clinical experience, clinical meaning, and risk perceptions and clinical recommendations for clinical situations involving a VUS. Fifty-seven of the eligible members responded. During the pre-test counseling session for a BRCA risk assessment patient, the vast majority of counselors (80.7%) mention VUS as a possible test result. Nearly half, 49.1%, report having given such a result to their patients at least one to four times. However, only 63.2% felt as though their patients understood the meaning of a VUS result. When asked to conclude the implication of a VUS and make medical management recommendations, the responses were varied. Nevertheless, a good proportion of counselors expressed the importance of testing other family members to help clarify the proband's risk and aid in medical management issues. Although the recent recommendations by the American College of Medical Genetics suggest standards for the interpretation of sequence variations, they do not provide guidelines for making clinical recommendations based on these variations. The results of this study reveal significant diversity in the personal interpretation of a VUS result, leading to various clinical recommendations, and suggest a need for clinical management recommendations as well.

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 microg/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.