Clinically available BH3 mimetic drugs targeting BCLXL and/or BCL2 (navitoclax and venetoclax, respectively) are effective in some hematologic malignancies, but have limited efficacy in solid tumors. This study aimed to identify combination therapies that exploit clinical BH3 mimetics for prostate cancer. Prostate cancer cells or xenografts were treated with BH3 mimetics as single agents or in combination with other agents, and effects on MCL1 and apoptosis were assessed. MCL1 was also targeted directly using RNAi, CRISPR, or an MCL1-specific BH3 mimetic, S63845. We initially found that MCL1 depletion or inhibition markedly sensitized prostate cancer cells to apoptosis mediated by navitoclax, but not venetoclax, and , indicating that they are primed to undergo apoptosis and protected by MCL1 and BCLXL. Small-molecule EGFR kinase inhibitors (erlotinib, lapatinib) also dramatically sensitized to navitoclax-mediated apoptosis, and this was associated with markedly increased proteasome-dependent degradation of MCL1. This increased MCL1 degradation appeared to be through a novel mechanism, as it was not dependent upon GSK3β-mediated phosphorylation and subsequent ubiquitylation by the ubiquitin ligases βTRCP and FBW7, or through other previously identified MCL1 ubiquitin ligases or deubiquitinases. Inhibitors targeting additional kinases (cabozantinib and sorafenib) similarly caused GSK3β-independent MCL1 degradation, and in combination with navitoclax drove apoptosis and These results show that prostate cancer cells are primed to undergo apoptosis and that cotargeting BCLXL and MCL1, directly or indirectly through agents that increase MCL1 degradation, can induce dramatic apoptotic responses. .
This work presents an automatically annotated fiber cluster (AAFC) method to enable identification of anatomically meaningful white matter structures from the whole brain tractography. The proposed method consists of 1) a study-specific whole brain white matter parcellation using a well-established data-driven groupwise fiber clustering pipeline to segment tractography into multiple fiber clusters, and 2) a novel cluster annotation method to automatically assign an anatomical tract annotation to each fiber cluster by employing cortical parcellation information across multiple subjects. The novelty of the AAFC method is that it leverages group-wise information about the fiber clusters, including their fiber geometry and cortical terminations, to compute a tract anatomical label for each cluster in an automated fashion. We demonstrate the proposed AAFC method in an application of investigating white matter abnormality in emotional processing and sensorimotor areas in major depressive disorder (MDD). Seven tracts of interest related to emotional processing and sensorimotor functions are automatically identified using the proposed AAFC method as well as a comparable method that uses a cortical parcellation alone. Experimental results indicate that our proposed method is more consistent in identifying the tracts across subjects and across hemispheres in terms of the number of fibers. In addition, we perform a between-group statistical analysis in 31 MDD patients and 62 healthy subjects on the identified tracts using our AAFC method. We find statistical differences in diffusion measures in local regions within a fiber tract (e.g. 4 fiber clusters within the identified left hemisphere cingulum bundle (consisting of 14 clusters) are significantly different between the two groups), suggesting the ability of our method in identifying potential abnormality specific to subdivisions of a white matter structure.
Background: Digital Imaging and Communications in Medicine (DICOM) is the standard for the representation, storage, and communication of medical images and related information. A DICOM file format and communication protocol for pathology have been defined; however, adoption by vendors and in the field is pending. Here, we implemented the essential aspects of the standard and assessed its capabilities and limitations in a multisite, multivendor healthcare network.
Methods: We selected relevant DICOM attributes, developed a program that extracts pixel data and pixel-related metadata, integrated patient and specimen-related metadata, populated and encoded DICOM attributes, and stored DICOM files. We generated the files using image data from four vendor-specific image file formats and clinical metadata from two departments with different laboratory information systems. We validated the generated DICOM files using recognized DICOM validation tools and measured encoding, storage, and access efficiency for three image compression methods. Finally, we evaluated storing, querying, and retrieving data over the web using existing DICOM archive software.
Results: Whole slide image data can be encoded together with relevant patient and specimen-related metadata as DICOM objects. These objects can be accessed efficiently from files or through RESTful web services using existing software implementations. Performance measurements show that the choice of image compression method has a major impact on data access efficiency. For lossy compression, JPEG achieves the fastest compression/decompression rates. For lossless compression, JPEG-LS significantly outperforms JPEG 2000 with respect to data encoding and decoding speed.
Conclusion: Implementation of DICOM allows efficient access to image data as well as associated metadata. By leveraging a wealth of existing infrastructure solutions, the use of DICOM facilitates enterprise integration and data exchange for digital pathology.
Multiparametric Magnetic Resonance Imaging (mpMRI) is widely used for characterizing prostate cancer. Standard of care use of mpMRI in clinic relies on visual interpretation of the images by an expert. mpMRI is also increasingly used as a quantitative imaging biomarker of the disease. Little is known about repeatability of such quantitative measurements, and no test-retest datasets have been available publicly to support investigation of the technical characteristics of the MRI-based quantification in the prostate. Here we present an mpMRI dataset consisting of baseline and repeat prostate MRI exams for 15 subjects, manually annotated to define regions corresponding to lesions and anatomical structures, and accompanied by region-based measurements. This dataset aims to support further investigation of the repeatability of mpMRI-derived quantitative prostate measurements, study of the robustness and reliability of the automated analysis approaches, and to support development and validation of new image analysis techniques. The manuscript can also serve as an example of the use of DICOM for standardized encoding of the image annotation and quantification results.
Therapeutic options for the treatment of glioblastoma remain inadequate despite concerted research efforts in drug development. Therapeutic failure can result from poor permeability of the blood-brain barrier, heterogeneous drug distribution, and development of resistance. Elucidation of relationships among such parameters could enable the development of predictive models of drug response in patients and inform drug development. Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib. Mass spectrometry images of erlotinib were registered to histology and magnetic resonance images in order to correlate drug distribution with tumor characteristics. Phosphoproteomics and immunohistochemistry were used to assess protein signaling in response to drug, and integrated with transcriptional response using mRNA sequencing. This comprehensive dataset provides simultaneous insight into pharmacokinetics and pharmacodynamics and indicates that erlotinib delivery to intracranial tumors is insufficient to inhibit EGFR tyrosine kinase signaling.
RATIONALE AND OBJECTIVES: Analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging is notable for the variability of calculated parameters. The purpose of this study was to evaluate the level of measurement variability and error/variability due to modeling in DCE magnetic resonance imaging parameters.
MATERIALS AND METHODS: Two prostate DCE scans were performed on 11 treatment-naïve patients with suspected or confirmed prostate peripheral zone cancer within an interval of less than two weeks. Tumor-suspicious and normal-appearing regions of interest (ROI) in the prostate peripheral zone were segmented. Different Tofts-Kety based models and different arterial input functions, with and without bolus arrival time (BAT) correction, were used to extract pharmacokinetic parameters. The percent repeatability coefficient (%RC) of fitted model parameters K, v, and k was calculated. Paired t-tests comparing parameters in tumor-suspicious ROIs and in normal-appearing tissue evaluated each parameter's sensitivity to pathology.
RESULTS: Although goodness-of-fit criteria favored the four-parameter extended Tofts-Kety model with the BAT correction included, the simplest two-parameter Tofts-Kety model overall yielded the best repeatability scores. The best %RC in the tumor-suspicious ROI was 63% for k, 28% for v and 83% for K . The best p values for discrimination between tissues were p <10 for k and K, and p = 0.11 for v. Addition of the BAT correction to the models did not improve repeatability.
CONCLUSION: The parameter k, using an arterial input functions directly measured from blood signals, was more repeatable than K. Both K and k values were highly discriminatory between healthy and diseased tissues in all cases. The parameter v had high repeatability but could not distinguish the two tissue types.
PURPOSE: While the interaction between a needle and the surrounding tissue is known to cause a significant targeting error in prostate biopsy leading to false-negative results, few studies have demonstrated how it impacts in the actual procedure. We performed a pilot study on robot-assisted MRI-guided prostate biopsy with an emphasis on the in-depth analysis of the needle-tissue interaction in-vivo. Methods: The data were acquired during in-bore transperineal prostate biopsies in patients using a 4 degrees-of-freedom (DoF) MRI-compatible robot. The anatomical structures in the pelvic area and the needle path were reconstructed from MR images, and quantitatively analyzed. We analyzed each structure individually and also proposed a mathematical model to investigate the influence of those structures in the targeting error using the mixed-model regression. Results: The median targeting error in 188 insertions (27 patients) was 6.3mm. Both the individual anatomical structure analysis and the mixed-model analysis showed that the deviation resulted from the contact between the needle and the skin as the main source of error. On contrary, needle bending inside the tissue (expressed as needle curvature) did not vary among insertions with targeting errors above and below the average. The analysis indicated that insertions crossing the bulbospongiosus presented a targeting error lower than the average. The mixed-model analysis demonstrated that the distance between the needle guide and the patient skin, the deviation at the entry point, and the path length inside the pelvic diaphragm had a statistically significant contribution to the targeting error (p<0.05). Conclusions: Our results indicate that the errors associated with the elastic contact between the needle and the skin were more prominent than the needle bending along the insertion. Our findings will help to improve the preoperative planning of transperineal prostate biopsies.
Conventional metabolomic methods include extensive sample preparation steps and long analytical run times, increasing the likelihood of processing artifacts and limiting high throughput applications. We present here in vitro liquid extraction surface analysis mass spectrometry (ivLESA-MS), a variation on LESA-MS, performed directly on adherent cells grown in 96-well cell culture plates. To accomplish this, culture medium was aspirated immediately prior to analysis, and metabolites were extracted using LESA from the cell monolayer surface, followed by nano-electrospray ionization and MS analysis in negative ion mode. We applied this platform to characterize and compare lipidomic profiles of multiple breast cancer cell lines growing in culture (MCF-7, ZR-75-1, MDA-MB-453, and MDA-MB-231) and revealed distinct and reproducible lipidomic signatures between the cell lines. Additionally, we demonstrated time-dependent processing artifacts, underscoring the importance of immediate analysis. ivLESA-MS represents a rapid in vitro metabolomic method, which precludes the need for quenching, cell harvesting, sample preparation, and chromatography, significantly shortening preparation and analysis time while minimizing processing artifacts. This method could be further adapted to test drugs in vitro in a high throughput manner.
There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high-end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.
The pointwise encoding time reduction with radial acquisition (PETRA) ultrashort echo time MR imaging sequence at 3T enables visualization of the facial nerve from the brain stem, through the temporal bone, to the stylomastoid foramen without intravenous contrast. Use of the PETRA sequence, or other ultrashort echo time sequences, should be considered in the MR imaging evaluation of certain skull base tumors and perhaps other facial nerve and temporal bone pathologies.
PURPOSE: Matching points that are derived from features or landmarks in image data is a key step in some medical imaging applications. Since most robust point matching algorithms claim to be able to deal with outliers, users may place high confidence in the matching result and use it without further examination. However, for tasks such as feature-based registration in image-guided neurosurgery, even a few mismatches, in the form of invalid displacement vectors, could cause serious consequences. As a result, having an effective tool by which operators can manually screen all matches for outliers could substantially benefit the outcome of those applications. METHODS: We introduce a novel variogram-based outlier screening method for vectors. The variogram is a powerful geostatistical tool for characterizing the spatial dependence of stochastic processes. Since the spatial correlation of invalid displacement vectors, which are considered as vector outliers, tends to behave differently than normal displacement vectors, they can be efficiently identified on the variogram. RESULTS: We validate the proposed method on 9 sets of clinically acquired ultrasound data. In the experiment, potential outliers are flagged on the variogram by one operator and further evaluated by 8 experienced medical imaging researchers. The matching quality of those potential outliers is approximately 1.5 lower, on a scale from 1 (bad) to 5 (good), than valid displacement vectors. CONCLUSION: The variogram is a simple yet informative tool. While being used extensively in geostatistical analysis, it has not received enough attention in the medical imaging field. We believe there is a good deal of potential for clinically applying the proposed outlier screening method. By way of this paper, we also expect researchers to find variogram useful in other medical applications that involve motion vectors analyses.
This work presents an anatomically curated white matter atlas to enable consistent white matter tract parcellation across different populations. Leveraging a well-established computational pipeline for fiber clustering, we create a tract-based white matter atlas including information from 100 subjects. A novel anatomical annotation method is proposed that leverages population-based brain anatomical information and expert neuroanatomical knowledge to annotate and categorize the fiber clusters. A total of 256 white matter structures are annotated in the proposed atlas, which provides one of the most comprehensive tract-based white matter atlases covering the entire brain to date. These structures are composed of 58 deep white matter tracts including major long range association and projection tracts, commissural tracts, and tracts related to the brainstem and cerebellar connections, plus 198 short and medium range superficial fiber clusters organized into 16 categories according to the brain lobes they connect. Potential false positive connections are annotated in the atlas to enable their exclusion from analysis or visualization. In addition, the proposed atlas allows for a whole brain white matter parcellation into 800 fiber clusters to enable whole brain connectivity analyses. The atlas and related computational tools are open-source and publicly available. We evaluate the proposed atlas using a testing dataset of 584 diffusion MRI scans from multiple independently acquired populations, across genders, the lifespan (1 day-82 years), and different health conditions (healthy control, neuropsychiatric disorders, and brain tumor patients). Experimental results show successful white matter parcellation across subjects from different populations acquired on multiple scanners, irrespective of age, gender or disease indications. Over 99% of the fiber tracts annotated in the atlas were detected in all subjects on average. One advantage in terms of robustness is that the tract-based pipeline does not require any cortical or subcortical segmentations, which can have limited success in young children and patients with brain tumors or other structural lesions. We believe this is the first demonstration of consistent automated white matter tract parcellation across the full lifespan from birth to advanced age.
We introduce an approach for image segmentation based on sparse correspondences between keypoints in testing and training images. Keypoints represent automatically identified distinctive image locations, where each keypoint correspondence suggests a transformation between images. We use these correspondences to transfer label maps of entire organs from the training images to the test image. The keypoint transfer algorithm includes three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ segmentations. We report segmentation results for abdominal organs in whole-body CT and MRI, as well as in contrast-enhanced CT and MRI. Our method offers a speed-up of about three orders of magnitude in comparison to common multi-atlas segmentation, while achieving an accuracy that compares favorably. Moreover, keypoint transfer does not require the registration to an atlas or a training phase. Finally, the method allows for the segmentation of scans with highly variable field-of-view.
Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal-HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal-HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT-HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi-tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast-moving extra-cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico-striatal pathways as a function of CAG-repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG-repeats, which connects the genetic abnormality (CAG-repeats) to an imaging-based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico-striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation.
A simple but general solution of Navier's equation for axisymmetric shear wave propagation in a homogeneous isotropic viscoelastic medium is presented. It is well-suited for use as a forward model for some acoustic radiation force impulse based shear wave elastography applications because it does not require precise knowledge of the strength of the source, nor its spatial or temporal distribution. Instead, it depends on two assumptions: (1) the source distribution is axisymmetric and confined to a small region near the axis of symmetry, and (2) the propagation medium is isotropic and homogeneous. The model accounts for the vector polarization of shear waves and exactly represents geometric spreading of the shear wavefield, whether spherical, cylindrical, or neither. It makes no assumption about the frequency dependence of material parameters, i.e., it is material-model independent. Validation using measured shear wavefields excited by acoustic radiation force in a homogeneous gelatin sample show that the model accounts for well over 90% of the measured wavefield "energy." An optimal fit of the model to simulated shear wavefields with noise in a homogeneous viscoelastic medium enables estimation of both the shear storage modulus and shear wave attenuation to within 1%.
PURPOSE: The brain undergoes significant structural change over the course of neurosurgery, including highly nonlinear deformation and resection. It can be informative to recover the spatial mapping between structures identified in preoperative surgical planning and the intraoperative state of the brain. We present a novel feature-based method for achieving robust, fully automatic deformable registration of intraoperative neurosurgical ultrasound images. METHODS: A sparse set of local image feature correspondences is first estimated between ultrasound image pairs, after which rigid, affine and thin-plate spline models are used to estimate dense mappings throughout the image. Correspondences are derived from 3D features, distinctive generic image patterns that are automatically extracted from 3D ultrasound images and characterized in terms of their geometry (i.e., location, scale, and orientation) and a descriptor of local image appearance. Feature correspondences between ultrasound images are achieved based on a nearest-neighbor descriptor matching and probabilistic voting model similar to the Hough transform. RESULTS: Experiments demonstrate our method on intraoperative ultrasound images acquired before and after opening of the dura mater, during resection and after resection in nine clinical cases. A total of 1620 automatically extracted 3D feature correspondences were manually validated by eleven experts and used to guide the registration. Then, using manually labeled corresponding landmarks in the pre- and post-resection ultrasound images, we show that our feature-based registration reduces the mean target registration error from an initial value of 3.3 to 1.5 mm. CONCLUSIONS: This result demonstrates that the 3D features promise to offer a robust and accurate solution for 3D ultrasound registration and to correct for brain shift in image-guided neurosurgery.
PURPOSE: Peritumoral edema impedes the full delineation of fiber tracts due to partial volume effects in image voxels that contain a mixture of cerebral parenchyma and extracellular water. The purpose of this study is to investigate the effect of incorporating a free water (FW) model of edema for white matter tractography in the presence of edema. MATERIALS AND METHODS: We retrospectively evaluated 26 consecutive brain tumor patients with diffusion MRI and T2-weighted images acquired presurgically. Tractography of the arcuate fasciculus (AF) was performed using the two-tensor unscented Kalman filter tractography (UKFt) method, the UKFt method with a reduced fiber tracking stopping fractional anisotropy (FA) threshold (UKFt+rFA), and the UKFt method with the addition of a FW compartment (UKFt+FW). An automated white matter fiber tract identification approach was applied to delineate the AF. Quantitative measurements included tract volume, edema volume, and mean FW fraction. Visual comparisons were performed by three experts to evaluate the quality of the detected AF tracts. RESULTS: The AF volume in edematous brain hemispheres was significantly larger using the UKFt+FW method (p<0.0001) compared to UKFt, but not significantly larger (p = 0.0996) in hemispheres without edema. The AF size increase depended on the volume of edema: a significant correlation was found between AF volume affected by (intersecting) edema and AF volume change with the FW model (Pearson r = 0.806, p<0.0001). The mean FW fraction was significantly larger in tracts intersecting edema (p = 0.0271). Compared to the UKFt+rFA method, there was a significant increase of the volume of the AF tract that intersected the edema using the UKFt+FW method, while the whole AF volumes were similar. Expert judgment results, based on the five patients with the smallest AF volumes, indicated that the expert readers generally preferred the AF tract obtained by using the FW model, according to their anatomical knowledge and considering the potential influence of the final results on the surgical route. CONCLUSION: Our results indicate that incorporating biophysical models of edema can increase the sensitivity of tractography in regions of peritumoral edema, allowing better tract visualization in patients with high grade gliomas and metastases.
OBJECTIVE Endoscopic endonasal approaches are increasingly performed for the surgical treatment of multiple skull base pathologies. Preventing postoperative CSF leaks remains a major challenge, particularly in extended approaches. In this study, the authors assessed the potential use of modern multimaterial 3D printing and neuronavigation to help model these extended defects and develop specifically tailored prostheses for reconstructive purposes. METHODS Extended endoscopic endonasal skull base approaches were performed on 3 human cadaveric heads. Preprocedure and intraprocedure CT scans were completed and were used to segment and design extended and tailored skull base models. Multimaterial models with different core/edge interfaces were 3D printed for implantation trials. A novel application of the intraoperative landmark acquisition method was used to transfer the navigation, helping to tailor the extended models. RESULTS Prostheses were created based on preoperative and intraoperative CT scans. The navigation transfer offered sufficiently accurate data to tailor the preprinted extended skull base defect prostheses. Successful implantation of the skull base prostheses was achieved in all specimens. The progressive flexibility gradient of the models' edges offered the best compromise for easy intranasal maneuverability, anchoring, and structural stability. Prostheses printed based on intraprocedure CT scans were accurate in shape but slightly undersized. CONCLUSIONS Preoperative 3D printing of patient-specific skull base models is achievable for extended endoscopic endonasal surgery. The careful spatial modeling and the use of a flexibility gradient in the design helped achieve the most stable reconstruction. Neuronavigation can help tailor preprinted prostheses.
Patient-mounted needle guide devices for percutaneous ablation are vulnerable to patient motion. The objective of this study is to develop and evaluate a software system for an MRI-compatible patient-mounted needle guide device that can adaptively compensate for displacement of the device due to patient motion using a novel image-based automatic device-to-image registration technique. We have developed a software system for an MRI-compatible patient-mounted needle guide device for percutaneous ablation. It features fully-automated image-based device-to-image registration to track the device position, and a device controller to adjust the needle trajectory to compensate for the displacement of the device. We performed: (a) a phantom study using a clinical MR scanner to evaluate registration performance; (b) simulations using intraoperative time-series MR data acquired in 20 clinical cases of MRI-guided renal cryoablations to assess its impact on motion compensation; and (c) a pilot clinical study in three patients to test its feasibility during the clinical procedure. FRE, TRE, and success rate of device-to-image registration were [Formula: see text] mm, [Formula: see text] mm, and 98.3% for the phantom images. The simulation study showed that the motion compensation reduced the targeting error for needle placement from 8.2 mm to 5.4 mm (p < 0.0005) in patients under general anesthesia (GA), and from 14.4 mm to 10.0 mm ([Formula: see text]) in patients under monitored anesthesia care (MAC). The pilot study showed that the software registered the device successfully in a clinical setting. Our simulation study demonstrated that the software system could significantly improve targeting accuracy in patients treated under both MAC and GA. Intraprocedural image-based device-to-image registration was feasible.
PURPOSE: To develop and evaluate an approach to estimate the respiratory-induced motion of lesions in the chest and abdomen. MATERIALS AND METHODS: The proposed approach uses the motion of an initial reference needle inserted into a moving organ to estimate the lesion (target) displacement that is caused by respiration. The needles position is measured using an inertial measurement unit (IMU) sensor externally attached to the hub of an initially placed reference needle. Data obtained from the IMU sensor and the target motion are used to train a learning-based approach to estimate the position of the moving target. An experimental platform was designed to mimic respiratory motion of the liver. Liver motion profiles of human subjects provided inputs to the experimental platform. Variables including the insertion angle, target depth, target motion velocity and target proximity to the reference needle were evaluated by measuring the error of the estimated target position and processing time. RESULTS: The mean error of estimation of the target position ranged between 0.86 and 1.29 mm. The processing maximum training and testing time was 5 ms which is suitable for real-time target motion estimation using the needle position sensor. CONCLUSION: The external motion of an initially placed reference needle inserted into a moving organ can be used as a surrogate, measurable and accessible signal to estimate in real-time the position of a moving target caused by respiration; this technique could then be used to guide the placement of subsequently inserted needles directly into the target.
Brain shift during tumor resection compromises the spatial validity of registered preoperative imaging data that is critical to image-guided procedures. One current clinical solution to mitigate the effects is to reimage using intraoperative magnetic resonance (iMR) imaging. Although iMR has demonstrated benefits in accounting for preoperative-to-intraoperative tissue changes, its cost and encumbrance have limited its widespread adoption. While iMR will likely continue to be employed for challenging cases, a cost-effective model-based brain shift compensation strategy is desirable as a complementary technology for standard resections. We performed a retrospective study of [Formula: see text] tumor resection cases, comparing iMR measurements with intraoperative brain shift compensation predicted by our model-based strategy, driven by sparse intraoperative cortical surface data. For quantitative assessment, homologous subsurface targets near the tumors were selected on preoperative MR and iMR images. Once rigidly registered, intraoperative shift measurements were determined and subsequently compared to model-predicted counterparts as estimated by the brain shift correction framework. When considering moderate and high shift ([Formula: see text], [Formula: see text] measurements per case), the alignment error due to brain shift reduced from [Formula: see text] to [Formula: see text], representing [Formula: see text] correction. These first steps toward validation are promising for model-based strategies.
OBJECTIVE: The purpose of this article is to report our intermediate to long-term outcomes with image-guided percutaneous hepatic tumor cryoablation and to evaluate its technical success, technique efficacy, local tumor progression, and adverse event rate. MATERIALS AND METHODS: Between 1998 and 2014, 299 hepatic tumors (243 metastases and 56 primary tumors; mean diameter, 2.5 cm; median diameter, 2.2 cm; range, 0.3-7.8 cm) in 186 patients (95 women; mean age, 60.9 years; range, 29-88 years) underwent cryoablation during 236 procedures using CT (n = 126), MRI (n = 100), or PET/CT (n = 10) guidance. Technical success, technique efficacy at 3 months, local tumor progression (mean follow-up, 2.5 years; range, 2 months to 14.6 years), and adverse event rates were calculated. RESULTS: The technical success rate was 94.6% (279/295). The technique efficacy rate was 89.5% (231/258) and was greater for tumors smaller than 4 cm (93.4%; 213/228) than for larger tumors (60.0%; 18/30) (p < 0.0001). Local tumor progression occurred in 23.3% (60/258) of tumors and was significantly more common after the treatment of tumors 4 cm or larger (63.3%; 19/30) compared with smaller tumors (18.0%; 41/228) (p < 0.0001). Adverse events followed 33.8% (80/236) of procedures and were grade 3-5 in 10.6% (25/236) of cases. Grade 3 or greater adverse events more commonly followed the treatment of larger tumors (19.5%; 8/41) compared with smaller tumors (8.7%; 17/195) (p = 0.04). CONCLUSION: Image-guided percutaneous cryoablation of hepatic tumors is efficacious; however, tumors smaller than 4 cm are more likely to be treated successfully and without an adverse event.
OBJECTIVE: We report nine consecutive percutaneous image-guided cryoablation procedures of head and neck tumors in seven patients (four men and three women; mean age, 68 years; age range, 50-78 years). Ablation of the entire tumor for local control or ablation of a region of tumor for pain relief or preservation of function was achieved in eight of nine procedures. One patient experienced intraprocedural bradycardia, and another developed a neopharyngeal abscess. There were no deaths, permanent neurologic or functional deficits, vascular complications, or adverse cosmetic sequelae due to the procedures. CONCLUSION: Percutaneous image-guided cryoablation offers a potentially less morbid minimally invasive treatment option than salvage head and neck surgery. The complications that we encountered may be avoidable with increased experience. Further work is needed to continue improving the safety and efficacy of cryoablation of head and neck tumors and to continue expanding the use of cryoablation in patients with head and neck tumors that cannot be treated surgically.