Prostate segmentation in transrectal ultrasound using magnetic resonance imaging priors

Purpose

In the current standard of care, real-time transrectal ultrasound (TRUS) is commonly used for prostate brachytherapy guidance. As TRUS provides limited soft tissue contrast, segmenting the prostate gland in TRUS images is often challenging and subject to inter-observer and intra-observer variability, especially at the base and apex where the gland boundary is hard to define. Magnetic resonance imaging (MRI) has higher soft tissue contrast allowing the prostate to be contoured easily. In this paper, we aim to show that prostate segmentation in TRUS images informed by MRI priors can improve on prostate segmentation that relies only on TRUS images.

Methods

First, we compare the TRUS-based prostate segmentation used in the treatment of 598 patients with a high-quality MRI prostate atlas and observe inconsistencies at the apex and base. Second, motivated by this finding, we propose an alternative TRUS segmentation technique that is fully automatic and uses MRI priors. The algorithm uses a convolutional neural network to segment the prostate in TRUS images at mid-gland, where the gland boundary can be clearly seen. It then reconstructs the gland boundary at the apex and base with the aid of a statistical shape model built from an MRI atlas of 78 patients.

Results

Compared to the clinical TRUS segmentation, our method achieves similar mid-gland segmentation results in the 598-patient database. For the seven patients who had both TRUS and MRI, our method achieved more accurate segmentation of the base and apex with the MRI segmentation used as ground truth.

Conclusion

Our results suggest that utilizing MRI priors in TRUS prostate segmentation could potentially improve the performance at base and apex.

     

Correlation of magnetic resonance imaging with digital histopathology in prostate

Purpose

We propose a systematic approach to correlate MRI and digital histopathology in prostate.

Methods

T2-weighted (T2W) MRI and diffusion-weighted imaging (DWI) are acquired, and a patient-specific mold (PSM) is designed from the MRI. Following prostatectomy, a whole mount tissue specimen is placed in the PSM and sectioned, ensuring that tissue blocks roughly correspond to MRI slices. Rigid body and thin plate spline deformable registration attempt to correct deformation during image acquisition and tissue preparation and achieve a more complete one-to-one correspondence between MRIs and tissue sections. Each tissue section is stained with hematoxylin and eosin and segmented by adopting a machine learning approach. Utilizing this tissue segmentation and image registration, the density of cellular and tissue components (lumen, nucleus, epithelium, and stroma) is estimated per MR voxel, generating density maps for the whole prostate.

Results

This study was approved by the local IRB, and informed consent was obtained from all patients. Registration of tissue specimens and MRIs was aided by the PSM and subsequent image registration. Tissue segmentation was performed using a machine learning approach, achieving \(\ge \)0.98 AUCs for lumen, nucleus, epithelium, and stroma. Examining the density map of tissue components, significant differences were observed between cancer, benign peripheral zone, and benign prostatic hyperplasia (p value \(<\)5e\(-\)2). Similarly, the signal intensity of the corresponding areas in both T2W MRI and DWI was significantly different (p value \(<\)1e\(-\)10).

Conclusions

The proposed approach is able to correlate MRI and digital histopathology of the prostate and is promising as a potential tool to facilitate a more cellular and zonal tissue-based analysis of prostate MRI, based upon a correlative histopathology perspective.

     

Accuracy analysis in MRI-guided robotic prostate biopsy

Purpose

To assess retrospectively the clinical accuracy of an magnetic resonance imaging-guided robotic prostate biopsy system that has been used in the US National Cancer Institute for over 6 years.

Methods

Series of 2D transverse volumetric MR image slices of the prostate both pre (high-resolution T2-weighted)- and post (low-resolution)- needle insertions were used to evaluate biopsy accuracy. A three-stage registration algorithm consisting of an initial two-step rigid registration followed by a B-spline deformable alignment was developed to capture prostate motion during biopsy. The target displacement (distance between planned and actual biopsy target), needle placement error (distance from planned biopsy target to needle trajectory), and biopsy error (distance from actual biopsy target to needle trajectory) were calculated as accuracy assessment.

Results

A total of 90 biopsies from 24 patients were studied. The registrations were validated by checking prostate contour alignment using image overlay, and the results were accurate to within 2 mm. The mean target displacement, needle placement error, and clinical biopsy error were 5.2, 2.5, and 4.3 mm, respectively.

Conclusion

The biopsy error reported suggests that quantitative imaging techniques for prostate registration and motion compensation may improve prostate biopsy targeting accuracy.

     

True Incidence of Gleason 6 Pathology in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Introduction

Recent evidence from histology studies regarding random prostate biopsies hint toward a relationship between higher biopsy Gleason score and the development of metastatic castration resistant prostate cancer (mCRPC). However, prostate biopsy underestimates final pathology in about one-third of patients. We evaluated the final whole gland pathology from radical prostatectomy exclusively in order to assess the true risk of progressing to the mCRPC state for patients with confirmed Gleason ≤6 prostate cancer.

Methods

Patients with confirmed mCRPC from our outpatient clinic were retrospectively evaluated with regard to whole gland pathology and the occurrence of Gleason 6 histology from 1995 to 2015. Conversely, patients with confirmed Gleason 6 pathology from our institutional database were followed up for the development of mCRPC from 2001 to 2015. Kaplan–Meier analysis and the log rank test were applied for survival analysis. The binomial test was used to evaluate occurrence rates of Gleason ≤6 pathologies in mCRPC patients.

Results

Out of 62 patients with mCRPC none had confirmed Gleason 6 pathology on whole gland histology of the prostate. Out of 86 patients with confirmed Gleason 6 pathology none developed an mCRPC over the follow-up period.

Conclusion

The development of mCRPC in patients with true Gleason 6 pathology is very rare and could not be confirmed in our series. This finding may have important implications in future treatment planning.

     

Vessel-based registration of an optical shape sensing catheter for MR navigation

Purpose

Magnetic resonance navigation (MRN), achieved with an upgraded MRI scanner, aims to guide therapeutic nanoparticles from their release in the hepatic vascular network to embolize highly vascularized liver tumors. Visualizing the catheter in real-time within the arterial network is important for selective embolization within the MR gantry. To achieve this, a new MR-compatible catheter tracking technology based on optical shape sensing is used.

Methods

This paper proposes a vessel-based registration pipeline to co-align this novel catheter tracking technology to the patient’s diagnostic MR angiography (MRA) with 3D roadmapping. The method first extracts the 3D hepatic arteries from a diagnostic MRA based on concurrent deformable models, creating a detailed representation of the patient’s internal anatomy. Once the optical shape sensing fibers, inserted in a double-lumen catheter, is guided into the hepatic arteries, the 3D centerline of the catheter is inferred and updated in real-time using strain measurements derived from fiber Bragg gratings sensors. Using both centerlines, a diffeomorphic registration based on a spectral representation of the high-level geometrical primitives is applied.

Results

Results show promise in registration accuracy in five phantom models created from stereolithography of patient-specific vascular anatomies, with maximum target registration errors below 2 mm. Furthermore, registration accuracy with the shape sensing tracking technology remains insensitive to the magnetic field of the MR magnet.

Conclusions

This study demonstrates that an accurate registration procedure of a shape sensing catheter with diagnostic imaging is feasible.

     

Basic study of less invasive high-intensity focused ultrasound (HIFU) in fetal therapy for twin reversed arterial perfusion (TRAP) sequence

Purpose

The objective of the present study was to develop a high-intensity focused ultrasound (HIFU) transducer more suitable for clinical use in fetal therapy for twin reversed arterial perfusion (TRAP) sequence.

Materials and methods

We created a cooling and degassed water-circulating-type HIFU treatment device. HIFU was applied to renal branch vessels in three rabbits. Sequential HIFU irradiation contains a trigger wave, heating wave, and rest time. The duration of HIFU application was 10 s/course. Targeting could be achieved by setting the imaging probe in the center and placing the HIFU beam and imaging ultrasonic wave on the same axis.

Result

We confirmed under sequential HIFU irradiation with a total intensity of 1.94 kW/cm² (spatial average temporal average intensity) that the vein and artery were occluded in all three rabbits.

Conclusion

Simultaneous occluding of the veins and arteries was confirmed with trigger waves and a resting phase using the HIFU transducer treatment device created for this study. Clinical application appears possible and may represent a promising option for fetal therapy involving TRAP sequence.

     

Fiducial-based fusion of 3D dental models with magnetic resonance imaging

Purpose

Magnetic resonance imaging (MRI) is widely used in study of maxillofacial structures. While MRI is the modality of choice for soft tissues, it fails to capture hard tissues such as bone and teeth. Virtual dental models, acquired by optical 3D scanners, are becoming more accessible for dental practice and are starting to replace the conventional dental impressions. The goal of this research is to fuse the high-resolution 3D dental models with MRI to enhance the value of imaging for applications where detailed analysis of maxillofacial structures are needed such as patient examination, surgical planning, and modeling.

Methods

A subject-specific dental attachment was digitally designed and 3D printed based on the subject’s face width and dental anatomy. The attachment contained 19 semi-ellipsoidal concavities in predetermined positions where oil-based ellipsoidal fiducial markers were later placed. The MRI was acquired while the subject bit on the dental attachment. The spatial position of the center of mass of each fiducial in the resultant MR Image was calculated by averaging its voxels’ spatial coordinates. The rigid transformation to fuse dental models to MRI was calculated based on the least squares mapping of corresponding fiducials and solved via singular-value decomposition.

Results

The target registration error (TRE) of the proposed fusion process, calculated in a leave-one-fiducial-out fashion, was estimated at 0.49 mm. The results suggest that 6–9 fiducials suffice to achieve a TRE of equal to half the MRI voxel size.

Conclusion

Ellipsoidal oil-based fiducials produce distinguishable intensities in MRI and can be used as registration fiducials. The achieved accuracy of the proposed approach is sufficient to leverage the merged 3D dental models with the MRI data for a finer analysis of the maxillofacial structures where complete geometry models are needed.

     

Magnetic Targeting and Delivery of Drug-Loaded SWCNTs Theranostic Nanoprobes to Lung Metastasis in Breast Cancer Animal Model: Noninvasive Monitoring Using Magnetic Resonance Imaging

Purpose

In this study, we aimed to develop novel therapeutic and diagnostic approaches by improving the targeting of doxorubicin-loaded single-walled carbon nanotubes (SWCNTs) to metastatic regions, and monitor their preferential homing and enhanced therapeutic effect using noninvasive free-breathing magnetic resonance imaging (MRI) and bioluminescence imaging.

Procedures

High-energy flexible magnets were specifically positioned over the metastatic tumor sites in the lungs. SWCNTs biodistribution, tumor progression, and subsequent treatment efficiency were assessed following administration of the magnetically attracted doxorubicin-loaded anti-CD105 conjugated nanocarriers.

Results

The use of high-energy magnets offered improved theranostic effect of doxorubicin-loaded nanocarriers, by magnetically targeting them towards metastatic tumor sites in the lungs. MRI allowed sensitive monitoring of nanocarriers biodistribution in the abdominal organs, their preferential homing towards the metastatic sites, and their enhanced therapeutic effect.

Conclusions

Combination of noninvasive MRI to localize sensitively the tumor sites, with specific positioning of magnets that can enhance the magnetic targeting of nanocarriers, allowed increasing the treatment efficiency.

     

Olanzapine vs haloperidol: treating delirium in a critical care setting

Objective

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.

Design

Prospective randomized trial

Setting

Tertiary care university affiliated critical care unit.

Patients

All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.

Interventions

Patients were randomized to receive either enteral olanzapine or haloperidol.

Measurements

Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.

Main results

Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.

Conclusions

Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

     

Estimating needle tip deflection in biological tissue from a single transverse ultrasound image: application to brachytherapy

Purpose

This paper proposes a method to predict the deflection of a flexible needle inserted into soft tissue based on the observation of deflection at a single point along the needle shaft.

Methods

We model the needle-tissue as a discretized structure composed of several virtual, weightless, rigid links connected by virtual helical springs whose stiffness coefficient is found using a pattern search algorithm that only requires the force applied at the needle tip during insertion and the needle deflection measured at an arbitrary insertion depth. Needle tip deflections can then be predicted for different insertion depths.

Results

Verification of the proposed method in synthetic and biological tissue shows a deflection estimation error of \(<\)2 mm for images acquired at 35 % or more of the maximum insertion depth, and decreases to 1 mm for images acquired closer to the final insertion depth. We also demonstrate the utility of the model for prostate brachytherapy, where in vivo needle deflection measurements obtained during early stages of insertion are used to predict the needle deflection further along the insertion process.

Conclusion

The method can predict needle deflection based on the observation of deflection at a single point. The ultrasound probe can be maintained at the same position during insertion of the needle, which avoids complications of tissue deformation caused by the motion of the ultrasound probe.

     

Validation of automated ultrasound-CT registration of vertebrae

Purpose

Image-guided spine surgery requires registration of the patient anatomy and preoperative computed tomography (CT) images. A technique for intraoperative ultrasound image registration to preoperative CT scans was developed and tested. Validation of the ultrasound-CT registration technique was performed using porcine cadavers.

Methods

An ultrasound-CT registration technique was evaluated using 18 thoracic and lumbar vertebrae of 3 porcine cadavers with 10 different sweep patterns for ultrasound acquisition. For each sweep pattern at each vertebra, 100 randomly simulated initial misalignments were introduced. Each misalignment was registered. The resulting registration transformations were compared to gold standard registrations based on implanted fiducials to assess accuracy and robustness of the technique.

Results

The orthogonal-sweep acquisition was found to perform best and yielded a registration accuracy of 1.65 mm across all vertebrae on all porcine cadavers, where 82.5% of the registrations resulted in target registration errors below the 2 mm threshold recommended by a joint report from the experts in the field. In addition, we found that registration accuracy varies by the sweep pattern and vertebral level, but neighboring vertebrae tend to result in statistically similar accuracy. Ultrasound-CT registration took an average of 2.5 min to run, and the total registration time per vertebra (also including time for ultrasound acquisition and reconstruction) is approximately 8 min.

Conclusions

A previously described ultrasound-CT registration technique yields clinically acceptable accuracy and robustness on multiple vertebrae across multiple porcine cadavers. The total registration time is shorter than that of surface point-based manual registration.

     

GRAPE: a graphical pipeline environment for image analysis in adaptive magnetic resonance imaging

Purpose

We present a platform, GRAphical Pipeline Environment (GRAPE), to facilitate the development of patient-adaptive magnetic resonance imaging (MRI) protocols.

Methods

GRAPE is an open-source project implemented in the Qt C++ framework to enable graphical creation, execution, and debugging of real-time image analysis algorithms integrated with the MRI scanner. The platform provides the tools and infrastructure to design new algorithms, and build and execute an array of image analysis routines, and provides a mechanism to include existing analysis libraries, all within a graphical environment. The application of GRAPE is demonstrated in multiple MRI applications, and the software is described in detail for both the user and the developer.

Results

GRAPE was successfully used to implement and execute three applications in MRI of the brain, performed on a 3.0-T MRI scanner: (i) a multi-parametric pipeline for segmenting the brain tissue and detecting lesions in multiple sclerosis (MS), (ii) patient-specific optimization of the 3D fluid-attenuated inversion recovery MRI scan parameters to enhance the contrast of brain lesions in MS, and (iii) an algebraic image method for combining two MR images for improved lesion contrast.

Conclusions

GRAPE allows graphical development and execution of image analysis algorithms for inline, real-time, and adaptive MRI applications.

     

A clinically applicable laser-based image-guided system for laparoscopic liver procedures

Purpose

Laser range scanners (LRS) allow performing a surface scan without physical contact with the organ, yielding higher registration accuracy for image-guided surgery (IGS) systems. However, the use of LRS-based registration in laparoscopic liver surgery is still limited because current solutions are composed of expensive and bulky equipment which can hardly be integrated in a surgical scenario.

Methods

In this work, we present a novel LRS-based IGS system for laparoscopic liver procedures. A triangulation process is formulated to compute the 3D coordinates of laser points by using the existing IGS system tracking devices. This allows the use of a compact and cost-effective LRS and therefore facilitates the integration into the laparoscopic setup. The 3D laser points are then reconstructed into a surface to register to the preoperative liver model using a multi-level registration process.

Results

Experimental results show that the proposed system provides submillimeter scanning precision and accuracy comparable to those reported in the literature. Further quantitative analysis shows that the proposed system is able to achieve a patient-to-image registration accuracy, described as target registration error, of \(3.2\pm 0.57\,\hbox {mm}\).

Conclusions

We believe that the presented approach will lead to a faster integration of LRS-based registration techniques in the surgical environment. Further studies will focus on optimizing scanning time and on the respiratory motion compensation.

     

Automated identification and reduction of artifacts in cine four-dimensional computed tomography (4DCT) images using respiratory motion model

Purpose

Four-dimensional computed tomography (4DCT) images are often marred by artifacts that substantially degrade image quality and confound image interpretation. Human observation remains the standard method of 4DCT artifact evaluation, which is time-consuming and subjective. We develop a method to automatically identify and reduce artifacts in cine 4DCT images.

Methods

We proposed an algorithm that consisted of two main stages: deformable image registration and respiratory motion simulation. Specifically, each 4DCT phase image was registered to the breath-holding CT image using the block-matching method, with erroneous spatial matches removed by the least median of squares filter and the full displacement vector field generated by the moving least squares interpolation. The lung’s respiratory motion trajectory was then recovered from the displacement vector field using the parameterized polynomial function, with fitting parameters estimated by combinatorial optimization. In this way, artifacts were located according to deviations between image points and their motion trajectories and further corrected based on position prediction.

Results

The mean spatial error (standard deviation) was 1.00 (0.85) mm after registration as opposed to 6.96 (4.61) mm before registration. In addition, we took human observation conducted by medical experts as the gold standard. The average sensitivity, specificity, and accuracy of the proposed method in artifact identification were 0.97, 0.84, and 0.89, respectively.

Conclusions

The proposed method identified and reduced artifacts accurately and automatically, providing an alternative way to analyze 4DCT image quality and to correct problematic images for radiation therapy.

     

Robust augmented reality guidance with fluorescent markers in laparoscopic surgery

Purpose

Laparoscopic interventions require the precise navigation of medical instruments through the patient’s body, while taking critical structures into account. Although numerous concepts have been proposed for displaying subsurface anatomical detail using augmented reality, clinical translation of these methods has suffered from a lack of robustness as well as from cumbersome integration into the clinical workflow. The purpose of this study was to investigate the feasibility of a new approach to intra-operative registration based on fluorescent markers.

Methods

The proposed approach to augmented reality visualization relies on metabolizable fluorescent markers that are attached to the target organ to guide a 2D/3D intra-operative registration algorithm. In an ex vivo porcine study, marker tracking performance is evaluated in the presence of smoke, blood, and tissue in the field of view of the endoscope.

Results

In contrast to state-of-the-art needle-shaped fiducial markers, the fluorescent markers can be reliably tracked when occluded by smoke, blood or tissue. This makes the new 2D/3D intra-operative registration approach considerably more robust than state-of-the-art marker-based methods.

Conclusion

As the concept can be smoothly integrated into the clinical workflow, its potential for application in clinical laparoscopy is high.