X-ray microtomosynthesis of unstained pathology tissue samples.

In pathology protocols, a tissue block, such as one containing a mouse brain or a biopsy sample from a patient, can produce several hundred thin sections. Substantial time may be required to analyse all sections. In cases of uncertainty regarding which sections to focus on, noninvasive scout imaging of intact blocks can help in guiding the pathology procedure. The scouting step is ideally done in a time window of minutes without special sample preparation that may interfere with the pathology procedures. The challenge is to obtain some visibility of unstained tissue structures at sub-10 µm resolution. We explored a novel x-ray tomosynthesis method as a way to maximise contrast-to-noise ratio, a determinant of tissue visibility. It provided a z-stack of thousands of images at 7.3 µm resolution (10% contrast, half-period of 68.5 line pairs/mm), in scans of 5-15 minutes. When compared with micro-CT scans, the straight-line tomosynthesis scan did not need to rotate the sample, which allowed flat samples, such as paraffin blocks, to be kept as close as possible to the x-ray source. Thus, given the same hardware, scan time and resolution, this mode maximised the photon flux density through the sample, which helped in maximising the contrast-to-noise ratio. The tradeoff of tomosynthesis is incomplete 3D information. The microtomosynthesis scanner has scanned 110 unstained human and animal tissue samples as part of their respective pathology protocols. In all cases, the z-stack of images showed tissue structures that guided sectioning or provided correlative structural information. We describe six examples that presented different levels of visibility of soft tissue structures. Additionally, in a set of coronary artery samples from an HIV patient donor, microtomosynthesis made a new discovery of isolated focal calcification in the internal elastic lamina of coronary wall, which was the onset of medial calcific sclerosis in the arteries.

A microscopy version of the imaging method for 3D luggage screening has been adapted to image unstained pathology samples. Pathology tests of tissue samples are used for clinical diagnosis and for biomedical research. The tissue samples are often embedded in paraffin blocks and sectioned into many thin slices, which are then stained with the appropriate agents for light microscopy. Since each tissue block can produce several hundred thin sections, much time and labour is required to analyse all sections. Noninvasive scout imaging of intact blocks can help in guiding the pathology procedure. The scouting step is ideally done in a time window of minutes without special sample preparation that may interfere with the pathology procedures. The challenge is to obtain some visibility of unstained tissue structures at sufficient resolution. X-ray imaging is a promising tool to meet the challenge since x-rays can penetrate thick samples that are opaque to visible light. With x-ray imaging, a determinant of tissue visibility is the flux density of photons that illuminate the sample. We explored a novel x-ray tomosynthesis method as a way to maximise this factor. It provided a stack of thousands of cross-sectional images at 7.3 µm resolution (half-period of 68.5 line pairs/mm) in scans of 5-15 minutes. When compared with micro-CT scans (a widely used laboratory technology), this method did not need to rotate the sample, which allowed flat samples such as paraffin blocks to be kept as close as possible to the x-ray source. Thus, given the same hardware, scan time and resolution, this method maximised the photon flux density through the sample, which helped in improving the visibility of unstained tissue under x-ray. The tradeoff of the method is incomplete 3D information. Over 100 unstained human and animal tissue samples have been scanned with this method as part of their respective pathology protocols. In all cases, the stack of cross-sectional images showed tissue structures that guided pathology analysis or provided correlative structural information. We describe six examples that presented different levels of tissue visibility. Additionally, in a set of coronary artery samples from an HIV patient donor, microtomosynthesis made a new discovery of isolated focal calcification in the internal elastic lamina of coronary wall, which was the onset of medial calcific sclerosis in the arteries.

Pathology of balloon-expandable and self-expanding stents following MRI-guided transapical aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Balloon-expandable (BE) and self-expanding (SE) prostheses are both used for transcatheter aortic valve replacement (TAVR), but differences in long-term outcome using these types of device are unknown. The study aim was to monitor the histopathology, echocardiographic findings and structural integrity of BE and SE stents in a preclinical model for up to six months after TAVR. METHODS: Real-time magnetic resonance imaging (rtMRI)-guided TAVR was performed in 22 Yucatan pigs using either a BE (n = 10) or a SE (n = 12) prosthesis. Follow up echocardiography and MRI studies were performed at one-, three-, and six-month intervals. Additionally, high-contrast radiography was used to assess for strut fractures. The pigs were sacrificed after six months and tissues taken for histopathologic analysis. RESULTS: Stent malapposition was found in seven BE prostheses (70%), and in three SE prostheses (25%) (p = 0.046). Three of the SE group (25%) had a partial left coronary artery obstruction. The incidence and severity of aortic regurgitation were similar between the BE and SE groups. Three BE prostheses (30%) and one SE prosthesis (8.3%) had a gap between the stent frame and aorta. The mean (±SD) number of strut fractures was 6.1 ± 3.45 and 1.17 ± 2.32 in the BE and SE groups, respectively (p = 0.002). In addition, two implanted BE prostheses (20%) had a consequential compressed stent frame appearance. CONCLUSION: Long-term pathologic examination of necropsy specimens from a preclinical model of rtMRI-guided TAVR showed SE stent prostheses to be superior to their BE counterparts in terms of correct valve apposition and durability. These results may be attributed to the differing deployment methods and associated expansion forces employed by the BE and SE stents.

Online Calibration of a Linear Micro Tomosynthesis Scanner.

In a linear tomosynthesis scanner designed for imaging histologic samples of several centimeters size at 10 µm resolution, the mechanical instability of the scanning stage (±10 µm) exceeded the resolution of the image system, making it necessary to determine the trajectory of the stage for each scan to avoid blurring and artifacts in the images that would arise from the errors in the geometric information used in 3D reconstruction. We present a method for online calibration by attaching a layer of randomly dispersed micro glass beads or calcium particles to the bottom of the sample stage. The method was based on a parametric representation of the rigid body motion of the sample stage-marker layer assembly. The marker layer was easy to produce and proven effective in the calibration procedure.

Online Geometric Calibration of a Hybrid CT System for Ultrahigh-Resolution Imaging.

A hybrid imaging system consisting of a standard computed tomography (CT) scanner and a low-profile photon-counting detector insert in contact with the patient's body has been used to produce ultrahigh-resolution images in a limited volume in chest scans of patients. The detector insert is placed on the patient bed as needed and not attached. Thus, its position and orientation in the scanner is dependent on the patient's position and scan settings. To allow accurate image reconstruction, we devised a method of determining the relative geometry of the detector insert and the CT scanner for each scan using fiducial markers. This method uses an iterative registration algorithm to align the markers in the reconstructed volume from the detector insert to that of the concurrent CT scan. After obtaining precise geometric information of the detector insert relative to the CT scanner, the two complementary sets of images are summed together to create a detailed image with reduced artifacts.

Finite Element Analysis of a Novel Aortic Valve Stent.

Worldwide, one of the leading causes of death for patients with cardiovascular disease is aortic valve failure or insufficiency as a result of calcification and cardiovascular disease. The surgical treatment consists of repair or total replacement of the aortic valve. Artificial aortic valve implantation via a percutaneous or endovascular procedure is the minimally invasive alternative to open chest surgery, and the only option for high-risk or older patients. Due to the complex anatomical location between the left ventricle and the aorta, there are still engineering design optimization challenges which influence the long-term durability of the valve. In this study we developed a computer model and performed a numerical analysis of an original self-expanding stent for transcatheter aortic valve in order to optimize its design and materials. The study demonstrates the current valve design could be a good alternative to the existing commercially available valve devices.

Regional Ultrahigh-Resolution Rescan in a Clinical Whole-Body CT Scanner Using a Contact Detector Insert.

Ultrahigh-resolution, low-dose rescans in a region of interest following a general screening computed tomography (CT) scan is motivated by the need to reduce invasive tissue biopsy procedures in cancer screening. We describe a new method to meet the conflicting demands of ultrahigh resolution, high-speed and ultralow-dose, and the first proof-of-concept experiment. With improving detector resolution, the limiting factor for the system resolution of whole-body CT scanners shifts to the penumbra of the source focal spot. The penumbra unsharpness is minimized by inserting flat-panel detector(s) that are in direct contact with the body. In the hybrid system, the detector insert and the CT detector acquire data simultaneously, whereby the standard CT images give the position and orientation of the detector insert(s) as needed for tomosynthesis reconstruction. Imaging tests were performed with a compact photon-counting detector insert on resolution targets of both high- and low-contrast as well as a mouse specimen, all inside a body phantom. Detector insert tomosynthesis provided twice the resolution of the CT scanner alone at the same dose concentration. The short 2-cm beam collimation of the tomosynthesis rescan gave an effective dose equivalent to 6% of an average CT scan in the chest or abdomen.

Spatiotemporal dissipative solitons in two-dimensional photonic lattices.

We analyze spatiotemporal dissipative solitons in two-dimensional photonic lattices in the presence of gain and loss. In the framework of the continuous-discrete cubic-quintic Ginzburg-Landau model, we demonstrate the existence of novel classes of two-dimensional spatiotemporal dissipative lattice solitons, which also include surface solitons located in the corners or at the edges of the truncated two-dimensional photonic lattice. We find the domains of existence and stability of such spatiotemporal dissipative solitons in the relevant parameter space, for both on-site and intersite lattice solitons. We show that the on-site solitons are stable in the whole domain of their existence, whereas most of the intersite solitons are unstable. We describe the scenarios of the instability-induced dynamics of dissipative solitons in two-dimensional lattices.

Novel Direct Annuloplasty Fastener System for Minimally Invasive Mitral Valve Repair.

The development of less invasive approaches for mitral valve repair remains an important objective, particularly in patients with multiple comorbidities. We describe a novel method to affix a mitral valve annuloplasty ring in a minimally invasive manner. A delivery apparatus for an annuloplasty fastener system was designed. Two channels were created, one for advancing the annuloplasty ring, and another to accommodate the fastener applicator. Custom designed fasteners, either with a helical-shaped screw or a strap-shaped tack structure, were tested. Fasteners were primed within an application device and automatic alignment of fasteners was achieved to allow accurate firing of the fixators securing the ring. The delivery apparatus was constructed to be deployed within a 10 mm trocar through a left atrial approach. Using a cadaveric swine heart model, access to the mitral valve from the left atrium was obtained with insertion of a trocar. The delivery apparatus was accurately directed to the mitral annulus under echocardiographic guidance. Fasteners were placed along the annular plane to secure the annuloplasty ring. Both fastener designs achieved considerable fixation force; the helical-shaped screw was found to have significantly greater fixation force compared to the strap-shaped tack design. The annuloplasty ring remained intact and did not experience any structural deformity during the fixation process. The use of a novel fastener system was successful in deploying and securing a mitral valve annuloplasty ring. These promising results may have further application for minimally invasive mitral valve repairs. Additional evaluation of this procedure with pre-clinical in vivo animal studies is necessary.

Stable discrete surface light bullets.

We analyze spatiotemporal light localization near the edge of a semi-infinite array of weakly coupled nonlinear optical waveguides and demonstrate the existence of a novel class of continuous-discrete spatiotemporal solitons, the so-called discrete surface light bullets. We show that their properties are strongly affected by the presence of the surface. To this end the crossover between surface and quasi-bulk bullets is studied by analyzing the families of solitons propagating at different distances from the edge of the waveguide array.

Spatiotemporal discrete surface solitons in binary waveguide arrays.

We study spatiotemporal solitons at the edge of a semi-infinite binary array of optical waveguides and, in particular, predict theoretically the existence of a novel type of surface soliton, the surface gap light bullets. We analyze the stability properties of these solitons in the framework of the continuous-discrete model of an array of two types of optical waveguides.

Real-time magnetic resonance imaging guidance for cardiovascular procedures.

Magnetic resonance imaging (MRI) of the cardiovascular system has proven to be an invaluable diagnostic tool. Given the ability to allow for real-time imaging, MRI guidance of intraoperative procedures can provide superb visualization, which can facilitate a variety of interventions and minimize the trauma of the operations as well. In addition to the anatomic detail, MRI can provide intraoperative assessment of organ and device function. Instruments and devices can be marked to enhance visualization and tracking, all of which is an advance over standard X-ray or ultrasonic imaging.

Automatic brachytherapy seed placement under MRI guidance.

The paper presents a robotic method of performing low dose rate prostate brachytherapy under magnetic resonance imaging (MRI) guidance. The design and operation of a fully automated MR compatible seed injector is presented. This is used with the MrBot robot for transperineal percutaneous prostate access. A new image-registration marker and algorithms are also presented. The system is integrated and tested with a 3T MRI scanner. Tests compare three different registration methods, assess the precision of performing automated seed deployment, and use the seeds to assess the accuracy of needle targeting under image guidance. Under the ideal conditions of the in vitro experiments, results show outstanding image-guided needle and seed placement accuracy.

An evaluation method for the mechanical performance of guide-wires and catheters in accessing the upper urinary tract.

The placement of guide-wires and catheters to gain access to the upper urinary tract can induce undesirable stresses on tissues. Previous studies have characterized the performance of wires and catheters by evaluating their physical properties such as stiffness and friction coefficient. However, the results of these studies do not directly quantify the wire's effects on tissues. Furthermore, the individual physical properties of wires and catheters investigated in previous studies cannot be simply summed up to characterize the behavior of an entire wire/catheter ensemble. This paper presents an objective method for testing guide-wires and catheters that estimates the forces applied by these instruments to anatomical structures during urological procedures. Our model utilizes a computer-controlled test stand that simulates a urological environment by including a tortuous path and a stone obstruction. Experimental results using this model show significant promise in reflecting the performance of guide-wires and catheters measuring the stress exerted upon relevant anatomical structures. Furthermore, due to the modularity of the approach, the model can be easily reconfigured to simulate environments relevant to other medical fields.

A New Type of Motor: Pneumatic Step Motor.

This paper presents a new type of pneumatic motor, a pneumatic step motor (PneuStep). Directional rotary motion of discrete displacement is achieved by sequentially pressurizing the three ports of the motor. Pulsed pressure waves are generated by a remote pneumatic distributor. The motor assembly includes a motor, gearhead, and incremental position encoder in a compact, central bore construction. A special electronic driver is used to control the new motor with electric stepper indexers and standard motion control cards. The motor accepts open-loop step operation as well as closed-loop control with position feedback from the enclosed sensor. A special control feature is implemented to adapt classic control algorithms to the new motor, and is experimentally validated. The speed performance of the motor degrades with the length of the pneumatic hoses between the distributor and motor. Experimental results are presented to reveal this behavior and set the expectation level. Nevertheless, the stepper achieves easily controllable precise motion unlike other pneumatic motors. The motor was designed to be compatible with magnetic resonance medical imaging equipment, for actuating an image-guided intervention robot, for medical applications. For this reason, the motors were entirely made of nonmagnetic and dielectric materials such as plastics, ceramics, and rubbers. Encoding was performed with fiber optics, so that the motors are electricity free, exclusively using pressure and light. PneuStep is readily applicable to other pneumatic or hydraulic precision-motion applications.

Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance.

BACKGROUND: Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. OBJECTIVES: This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. METHODS: In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. RESULTS: In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). CONCLUSIONS: Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.

Robotically assisted prostate brachytherapy with transrectal ultrasound guidance--Phantom experiments.

PURPOSE: To report the preliminary experimental results obtained with a robot-assisted transrectal ultrasound (TRUS)-guided prostate brachytherapy system. METHODS AND MATERIALS: The system consists of a TRUS unit, a spatially coregistered needle insertion robot, and an FDA-approved treatment planning and image-registered implant system. The robot receives each entry/target coordinate pair of the implant plan, inserts a preloaded needle, and then the seeds are deposited. The needles/sources are tracked in TRUS, thus allowing the plan to be updated as the procedure progresses. RESULTS: The first insertion attempt was recorded for each needle, without adjustment. All clinically relevant locations were reached in a prostate phantom. Nonparallel and parallel needle trajectories were demonstrated. Based on TRUS, the average transverse placement error was 2 mm (worst case 2.5 mm, 80% less than 2 mm), and the average sagittal error was 2.5 mm (worst case 5.0 mm, 70% less than 2.5 mm). CONCLUSIONS: The concept and technical viability of robot-assisted brachytherapy were demonstrated in phantoms. The kinematically decoupled robotic assistant device is inherently safe. Overall performance was promising, but further optimization is necessary to prove the possibility of improved dosimetry.

Synthetic torso for training in and evaluation of urologic laparoscopic skills.

BACKGROUND: The expanding use of advanced minimally invasive surgical techniques demands more advanced training methods, objective measures of resident performance, and more realistic and anatomically correct training models. MATERIALS AND METHODS: A new synthetic torso for urologic laparoscopy training was developed and assessed. The trainer, Lapman, was based on the Visible Human Model and has the exact shape of a human torso. The torso models the outer shape of the body and the abdominal and pulmonary cavities. Animal or synthetic models of the abdominal organs may be placed in the abdominal cavity. An abdominal wall provides access and seals the cavity and can be replaced after repeated punctures with laparoscopic instruments. The thoracic cavity connects to a pneumatic pump to simulate breathing. In order to render realistic mechanic properties, the torso is cast of materials with elastic properties similar to those of soft tissue and incorporates a synthetic skeleton. These similar mechanical properties and the thoracic insufflation create realistic ventilatory motion simulation. RESULTS: Twenty-five individuals--medical students, residents, and attending urologists--participated in a study comparing Lapman with a standard training box. Lapman presented several advantages over the traditional training box, specifically with regard to internal and external views and the incorporation of a realistically shaped abdominal wall. A significant and recurrent theme was the value of the synthetic wall as a tool to gain a greater appreciation of the importance of port placement. Study participants at all levels of training appreciated that Lapman gives a more realistic approximation of the operative procedure. CONCLUSIONS: The novelty of the trainer consists in its anatomic shape, realistic mechanical properties, and ventilatory simulation. This paper reports on its design, construction, and preliminary tests.

Real-time magnetic resonance imaging-guided transcatheter aortic valve replacement.

OBJECTIVES: To demonstrate the feasibility of Real-time magnetic resonance imaging (rtMRI) guided transcatheter aortic valve replacement (TAVR) with an active guidewire and an MRI compatible valve delivery catheter system in a swine model. METHODS: The CoreValve system was minimally modified to be MRI-compatible by replacing the stainless steel components with fluoroplastic resin and high-density polyethylene components. Eight swine weighing 60-90 kg underwent rtMRI-guided TAVR with an active guidewire through a left subclavian approach. RESULTS: Two imaging planes (long-axis view and short-axis view) were used simultaneously for real-time imaging during implantation. Successful deployment was performed without rapid ventricular pacing or cardiopulmonary bypass. Postdeployment images were acquired to evaluate the final valve position in addition to valvular and cardiac function. CONCLUSIONS: Our results show that the CoreValve can be easily and effectively deployed through a left subclavian approach using rtMRI guidance, a minimally modified valve delivery catheter system, and an active guidewire. This method allows superior visualization before deployment, thereby allowing placement of the valve with pinpoint accuracy. rtMRI has the added benefit of the ability to perform immediate postprocedural functional assessment, while eliminating the morbidity associated with radiation exposure, rapid ventricular pacing, contrast media renal toxicity, and a more invasive procedure. Use of a commercially available device brings this rtMRI-guided approach closer to clinical reality.

Robot-assisted real-time magnetic resonance image-guided transcatheter aortic valve replacement.

BACKGROUND: Real-time magnetic resonance imaging (rtMRI)-guided transcatheter aortic valve replacement (TAVR) offers improved visualization, real-time imaging, and pinpoint accuracy with device delivery. Unfortunately, performing a TAVR in a MRI scanner can be a difficult task owing to limited space and an awkward working environment. Our solution was to design a MRI-compatible robot-assisted device to insert and deploy a self-expanding valve from a remote computer console. We present our preliminary results in a swine model. METHODS: We used an MRI-compatible robotic arm and developed a valve delivery module. A 12-mm trocar was inserted in the apex of the heart via a subxiphoid incision. The delivery device and nitinol stented prosthesis were mounted on the robot. Two continuous real-time imaging planes provided a virtual real-time 3-dimensional reconstruction. The valve was deployed remotely by the surgeon via a graphic user interface. RESULTS: In this acute nonsurvival study, 8 swine underwent robot-assisted rtMRI TAVR for evaluation of feasibility. Device deployment took a mean of 61 ± 5 seconds. Postdeployment necropsy was performed to confirm correlations between imaging and actual valve positions. CONCLUSIONS: These results demonstrate the feasibility of robotic-assisted TAVR using rtMRI guidance. This approach may eliminate some of the challenges of performing a procedure while working inside of an MRI scanner, and may improve the success of TAVR. It provides superior visualization during the insertion process, pinpoint accuracy of deployment, and, potentially, communication between the imaging device and the robotic module to prevent incorrect or misaligned deployment.

Robotic-assisted real-time MRI-guided TAVR: from system deployment to in vivo experiment in swine model.

PURPOSE: Real-time magnetic resonance imaging (rtMRI) guidance provides significant advantages during transcatheter aortic valve replacement (TAVR) as it provides superior real-time visualization and accurate device delivery tracking. However, performing a TAVR within an MRI scanner remains difficult due to a constrained procedural environment. To address these concerns, a magnetic resonance (MR)-compatible robotic system to assist in TAVR deployments was developed. This study evaluates the technical design and interface considerations of an MR-compatible robotic-assisted TAVR system with the purpose of demonstrating that such a system can be developed and executed safely and precisely in a preclinical model. METHODS: An MR-compatible robotic surgical assistant system was built for TAVR deployment. This system integrates a 5-degrees of freedom (DoF) robotic arm with a 3-DoF robotic valve delivery module. A user interface system was designed for procedural planning and real-time intraoperative manipulation of the robot. The robotic device was constructed of plastic materials, pneumatic actuators, and fiber-optical encoders. RESULTS: The mechanical profile and MR compatibility of the robotic system were evaluated. The system-level error based on a phantom model was 1.14 ± 0.33 mm. A self-expanding prosthesis was successfully deployed in eight Yorkshire swine under rtMRI guidance. Post-deployment imaging and necropsy confirmed placement of the stent within 3 mm of the aortic valve annulus. CONCLUSIONS: These phantom and in vivo studies demonstrate the feasibility and advantages of robotic-assisted TAVR under rtMRI guidance. This robotic system increases the precision of valve deployments, diminishes environmental constraints, and improves the overall success of TAVR.