Deformable registration of preoperative MR and intraoperative long-length tomosynthesis images for guidance of spine surgery via image synthesis.

PURPOSE: Improved integration and use of preoperative imaging during surgery hold significant potential for enhancing treatment planning and instrument guidance through surgical navigation. Despite its prevalent use in diagnostic settings, MR imaging is rarely used for navigation in spine surgery. This study aims to leverage MR imaging for intraoperative visualization of spine anatomy, particularly in cases where CT imaging is unavailable or when minimizing radiation exposure is essential, such as in pediatric surgery. METHODS: This work presents a method for deformable 3D-2D registration of preoperative MR images with a novel intraoperative long-length tomosynthesis imaging modality (viz., Long-Film [LF]). A conditional generative adversarial network is used to translate MR images to an intermediate bone image suitable for registration, followed by a model-based 3D-2D registration algorithm to deformably map the synthesized images to LF images. The algorithm's performance was evaluated on cadaveric specimens with implanted markers and controlled deformation, and in clinical images of patients undergoing spine surgery as part of a large-scale clinical study on LF imaging. RESULTS: The proposed method yielded a median 2D projection distance error of 2.0 mm (interquartile range [IQR]: 1.1-3.3 mm) and a 3D target registration error of 1.5 mm (IQR: 0.8-2.1 mm) in cadaver studies. Notably, the multi-scale approach exhibited significantly higher accuracy compared to rigid solutions and effectively managed the challenges posed by piecewise rigid spine deformation. The robustness and consistency of the method were evaluated on clinical images, yielding no outliers on vertebrae without surgical instrumentation and 3% outliers on vertebrae with instrumentation. CONCLUSIONS: This work constitutes the first reported approach for deformable MR to LF registration based on deep image synthesis. The proposed framework provides access to the preoperative annotations and planning information during surgery and enables surgical navigation within the context of MR images and/or dual-plane LF images.

Combining physics-based models with deep learning image synthesis and uncertainty in intraoperative cone-beam CT of the brain.

BACKGROUND: Image-guided neurosurgery requires high localization and registration accuracy to enable effective treatment and avoid complications. However, accurate neuronavigation based on preoperative magnetic resonance (MR) or computed tomography (CT) images is challenged by brain deformation occurring during the surgical intervention. PURPOSE: To facilitate intraoperative visualization of brain tissues and deformable registration with preoperative images, a 3D deep learning (DL) reconstruction framework (termed DL-Recon) was proposed for improved intraoperative cone-beam CT (CBCT) image quality. METHODS: The DL-Recon framework combines physics-based models with deep learning CT synthesis and leverages uncertainty information to promote robustness to unseen features. A 3D generative adversarial network (GAN) with a conditional loss function modulated by aleatoric uncertainty was developed for CBCT-to-CT synthesis. Epistemic uncertainty of the synthesis model was estimated via Monte Carlo (MC) dropout. Using spatially varying weights derived from epistemic uncertainty, the DL-Recon image combines the synthetic CT with an artifact-corrected filtered back-projection (FBP) reconstruction. In regions of high epistemic uncertainty, DL-Recon includes greater contribution from the FBP image. Twenty paired real CT and simulated CBCT images of the head were used for network training and validation, and experiments evaluated the performance of DL-Recon on CBCT images containing simulated and real brain lesions not present in the training data. Performance among learning- and physics-based methods was quantified in terms of structural similarity (SSIM) of the resulting image to diagnostic CT and Dice similarity metric (DSC) in lesion segmentation compared to ground truth. A pilot study was conducted involving seven subjects with CBCT images acquired during neurosurgery to assess the feasibility of DL-Recon in clinical data. RESULTS: CBCT images reconstructed via FBP with physics-based corrections exhibited the usual challenges to soft-tissue contrast resolution due to image non-uniformity, noise, and residual artifacts. GAN synthesis improved image uniformity and soft-tissue visibility but was subject to error in the shape and contrast of simulated lesions that were unseen in training. Incorporation of aleatoric uncertainty in synthesis loss improved estimation of epistemic uncertainty, with variable brain structures and unseen lesions exhibiting higher epistemic uncertainty. The DL-Recon approach mitigated synthesis errors while maintaining improvement in image quality, yielding 15%-22% increase in SSIM (image appearance compared to diagnostic CT) and up to 25% increase in DSC in lesion segmentation compared to FBP. Clear gains in visual image quality were also observed in real brain lesions and in clinical CBCT images. CONCLUSIONS: DL-Recon leveraged uncertainty estimation to combine the strengths of DL and physics-based reconstruction and demonstrated substantial improvements in the accuracy and quality of intraoperative CBCT. The improved soft-tissue contrast resolution could facilitate visualization of brain structures and support deformable registration with preoperative images, further extending the utility of intraoperative CBCT in image-guided neurosurgery.

Deformable 3D-2D image registration and analysis of global spinal alignment in long-length intraoperative spine imaging.

BACKGROUND: Spinal deformation during surgical intervention (caused by patient positioning and/or the correction of malalignment) confounds conventional navigation due to the assumptions of rigid transformation. Moreover, the ability to accurately quantify spinal alignment in the operating room would provide an assessment of the surgical product via metrics that correlate with clinical outcomes. PURPOSE: A method for deformable 3D-2D registration of preoperative CT to intraoperative long-length tomosynthesis images is reported for an accurate 3D evaluation of device placement in the presence of spinal deformation and automated evaluation of global spinal alignment (GSA). METHODS: Long-length tomosynthesis ("Long Film," LF) images were acquired using an O-arm imaging system (Medtronic, Minneapolis USA). A deformable 3D-2D patient registration was developed using multi-scale masking (proceeding from the full-length image to local subvolumes about each vertebra) to transform vertebral labels and planning information from preoperative CT to the LF images. Automatic measurement of GSA (main thoracic kyphosis [MThK] and lumbar lordosis [LL]) was obtained using a spline fit to registered labels. The "Known-Component Registration" method for device registration was adapted to the multi-scale process for 3D device localization from orthogonal LF images. The multi-scale framework was evaluated using a deformable spine phantom in which pedicle screws were inserted, and deformations were induced over a range in LL ∼25°-80°. Further validation was carried out in a cadaver study with implanted pedicle screws and a similar range of spinal deformation. The accuracy of patient and device registration was evaluated in terms of 3D translational error and target registration error, respectively, and the accuracies of automatic GSA measurements were compared to manual annotation. RESULTS: Phantom studies demonstrated accurate registration via the multi-scale framework for all vertebral levels in both the neutral and deformed spine: median (interquartile range, IQR) patient registration error was 1.1 mm (0.7-1.9 mm IQR). Automatic measures of MThK and LL agreed with manual delineation within -1.1° ± 2.2° and 0.7° ± 2.0° (mean and standard deviation), respectively. Device registration error was 0.7 mm (0.4-1.0 mm IQR) at the screw tip and 0.9° (1.0°-1.5°) about the screw trajectory. Deformable 3D-2D registration significantly outperformed conventional rigid registration (p < 0.05), which exhibited device registration errors of 2.1 mm (0.8-4.1 mm) and 4.1° (1.2°-9.5°). Cadaver studies verified performance under realistic conditions, demonstrating patient registration error of 1.6 mm (0.9-2.1 mm); MThK within -4.2° ± 6.8° and LL within 1.7° ± 3.5°; and device registration error of 0.8 mm (0.5-1.9 mm) and 0.7° (0.4°-1.2°) for the multi-scale deformable method, compared to 2.5 mm (1.0-7.9 mm) and 2.3° (1.6°-8.1°) for rigid registration (p < 0.05). CONCLUSION: The deformable 3D-2D registration framework leverages long-length intraoperative imaging to achieve accurate patient and device registration over the extended lengths of the spine (up to 64 cm) even with strong anatomical deformation. The method offers a new means for the quantitative validation of spinal correction (intraoperative GSA measurement) and the 3D verification of device placement in comparison to preoperative images and planning data.

Pre-Clinical Development of Robot-Assisted Ventriculoscopy for 3D Image Reconstruction and Guidance of Deep Brain Neurosurgery.

Conventional neuro-navigation can be challenged in targeting deep brain structures via transventricular neuroendoscopy due to unresolved geometric error following soft-tissue deformation. Current robot-assisted endoscopy techniques are fairly limited, primarily serving to planned trajectories and provide a stable scope holder. We report the implementation of a robot-assisted ventriculoscopy (RAV) system for 3D reconstruction, registration, and augmentation of the neuroendoscopic scene with intraoperative imaging, enabling guidance even in the presence of tissue deformation and providing visualization of structures beyond the endoscopic field-of-view. Phantom studies were performed to quantitatively evaluate image sampling requirements, registration accuracy, and computational runtime for two reconstruction methods and a variety of clinically relevant ventriculoscope trajectories. A median target registration error of 1.2 mm was achieved with an update rate of 2.34 frames per second, validating the RAV concept and motivating translation to future clinical studies.

Technical assessment of 2D and 3D imaging performance of an IGZO-based flat-panel X-ray detector.

BACKGROUND: Indirect detection flat-panel detectors (FPDs) consisting of hydrogenated amorphous silicon (a-Si:H) thin-film transistors (TFTs) are a prevalent technology for digital x-ray imaging. However, their performance is challenged in applications requiring low exposure levels, high spatial resolution, and high frame rate. Emerging FPD designs using metal oxide TFTs may offer potential performance improvements compared to FPDs based on a-Si:H TFTs. PURPOSE: This work investigates the imaging performance of a new indium gallium zinc oxide (IGZO) TFT-based detector in 2D fluoroscopy and 3D cone-beam CT (CBCT). METHODS: The new FPD consists of a sensor array combining IGZO TFTs with a-Si:H photodiodes and a 0.7-mm thick CsI:Tl scintillator. The FPD was implemented on an x-ray imaging bench with system geometry emulating intraoperative CBCT. A conventional FPD with a-Si:H TFTs and a 0.6-mm thick CsI:Tl scintillator was similarly implemented as a basis of comparison. 2D imaging performance was characterized in terms of electronic noise, sensitivity, linearity, lag, spatial resolution (modulation transfer function, MTF), image noise (noise-power spectrum, NPS), and detective quantum efficiency (DQE) with entrance air kerma (EAK) ranging from 0.3 to 1.2 µGy. 3D imaging performance was evaluated in terms of the 3D MTF and noise-equivalent quanta (NEQ), soft-tissue contrast-to-noise ratio (CNR), and image quality evident in anthropomorphic phantoms for a range of anatomical sites and dose, with weighted air kerma, K w ${K_w}$ , ranging from 0.8 to 4.9 mGy. RESULTS: The 2D imaging performance of the IGZO-based FPD exhibited up to ∼1.7× lower electronic noise than the a-Si:H FPD at matched pixel pitch. Furthermore, the IGZO FPD exhibited ∼27% increase in mid-frequency DQE (1 mm-1 ) at matched pixel size and dose (EAK ≈ 1.0 µGy) and ∼11% increase after adjusting for differences in scintillator thickness. 2D spatial resolution was limited by the scintillator for each FPD. The IGZO-based FPD demonstrated improved 3D NEQ at all spatial frequencies in both head (≥25% increase for all dose levels) and body (≥10% increase for K w ${K_w}$ ≤2 mGy) imaging scenarios. These characteristics translated to improved low-contrast visualization in anthropomorphic phantoms, demonstrating ≥10% improvement in CNR and extension of the low-dose range for which the detector is input-quantum limited. CONCLUSION: The IGZO-based FPD demonstrated improvements in electronic noise, image lag, and NEQ that translated to measurable improvements in 2D and 3D imaging performance compared to a conventional FPD based on a-Si:H TFTs. The improvements are most beneficial for 2D or 3D imaging scenarios involving low-dose and/or high-frame rate.

Intraoperative cone-beam and slot-beam CT: 3D image quality and dose with a slot collimator on the O-arm imaging system.

PURPOSE: To characterize the 3D imaging performance and radiation dose for a prototype slot-beam configuration on an intraoperative O-arm™ Surgical Imaging System (Medtronic Inc., Littleton, MA) and identify potential improvements in soft-tissue image quality for surgical interventions. METHODS: A slot collimator was integrated with the O-arm™ system for slot-beam axial CT. The collimator can be automatically actuated to provide 1.2° slot-beam longitudinal collimation. Cone-beam and slot-beam configurations were investigated with and without an antiscatter grid (12:1 grid ratio, 60 lines/cm). Dose, scatter, image noise, and soft-tissue contrast resolution were evaluated in quantitative phantoms for head and body configurations over a range of exposure levels (beam energy and mAs), with reconstruction performed via filtered-backprojection. Qualitative imaging performance across various anatomical sites and imaging tasks was assessed with anthropomorphic head, abdomen, and pelvis phantoms. RESULTS: The dose for a slot-beam scan varied from 0.02-0.06 mGy/mAs for head protocols to 0.01-0.03 mGy/mAs for body protocols, yielding dose reduction by ∼1/5 to 1/3 compared to cone-beam, owing to beam collimation and reduced x-ray scatter. The slot-beam provided an ∼6-7× reduction in scatter-to-primary ratio (SPR) compared to the cone-beam, yielding SPR ∼20-80% for head and body without the grid and ∼7-30% with the grid. Compared to cone-beam scans at equivalent dose, slot-beam images exhibited an ∼2.5× increase in soft-tissue contrast-to-noise ratio (CNR) for both grid and gridless configurations. For slot-beam scans, a further ∼10-30% improvement in CNR was achieved when the grid was removed. Slot-beam imaging could benefit certain interventional scenarios in which improved visualization of soft tissues is required within a fairly narrow longitudinal region of interest ( ± 7 mm in z )--for example, checking the completeness of tumor resection, preservation of adjacent anatomy, or detection of complications (e.g., hemorrhage). While preserving existing capabilities for fluoroscopy and cone-beam CT, slot-beam scanning could enhance the utility of intraoperative imaging and provide a useful mode for safety and validation checks in image-guided surgery. CONCLUSIONS: The 3D imaging performance and dose of a prototype slot-beam CT configuration on the O-arm™ system was investigated. Substantial improvements in soft-tissue image quality and reduction in radiation dose are evident with the slot-beam configuration due to reduced x-ray scatter.

Sinogram + image domain neural network approach for metal artifact reduction in low-dose cone-beam computed tomography.

Purpose: Cone-beam computed tomography (CBCT) is commonly used in the operating room to evaluate the placement of surgical implants in relation to critical anatomical structures. A particularly problematic setting, however, is the imaging of metallic implants, where strong artifacts can obscure visualization of both the implant and surrounding anatomy. Such artifacts are compounded when combined with low-dose imaging techniques such as sparse-view acquisition. Approach: This work presents a dual convolutional neural network approach, one operating in the sinogram domain and one in the reconstructed image domain, that is specifically designed for the physics and setting of intraoperative CBCT to address the sources of beam hardening and sparse view sampling that contribute to metal artifacts. The networks were trained with images from cadaver scans with simulated metal hardware. Results: The trained networks were tested on images of cadavers with surgically implanted metal hardware, and performance was compared with a method operating in the image domain alone. While both methods removed most image artifacts, superior performance was observed for the dual-convolutional neural network (CNN) approach in which beam-hardening and view sampling effects were addressed in both the sinogram and image domain. Conclusion: The work demonstrates an innovative approach for eliminating metal and sparsity artifacts in CBCT using a dual-CNN framework which does not require a metal segmentation.

Long-length tomosynthesis and 3D-2D registration for intraoperative assessment of spine instrumentation.

PURPOSE: A system for long-length intraoperative imaging is reported based on longitudinal motion of an O-arm gantry featuring a multi-slot collimator. We assess the utility of long-length tomosynthesis and the geometric accuracy of 3D image registration for surgical guidance and evaluation of long spinal constructs. METHODS: A multi-slot collimator with tilted apertures was integrated into an O-arm system for long-length imaging. The multi-slot projective geometry leads to slight view disparity in both long-length projection images (referred to as 'line scans') and tomosynthesis 'slot reconstructions' produced using a weighted-backprojection method. The radiation dose for long-length imaging was measured, and the utility of long-length, intraoperative tomosynthesis was evaluated in phantom and cadaver studies. Leveraging the depth resolution provided by parallax views, an algorithm for 3D-2D registration of the patient and surgical devices was adapted for registration with line scans and slot reconstructions. Registration performance using single-plane or dual-plane long-length images was evaluated and compared to registration accuracy achieved using standard dual-plane radiographs. RESULTS: Longitudinal coverage of ∼50-64 cm was achieved with a single long-length slot scan, providing a field-of-view (FOV) up to (40 × 64) cm2, depending on patient positioning. The dose-area product (reference point air kerma × x-ray field area) for a slot scan ranged from ∼702-1757 mGy·cm2, equivalent to ∼2.5 s of fluoroscopy and comparable to other long-length imaging systems. Long-length scanning produced high-resolution tomosynthesis reconstructions, covering ∼12-16 vertebral levels. 3D image registration using dual-plane slot reconstructions achieved median target registration error (TRE) of 1.2 mm and 0.6° in cadaver studies, outperforming registration to dual-plane line scans (TRE = 2.8 mm and 2.2°) and radiographs (TRE = 2.5 mm and 1.1°). 3D registration using single-plane slot reconstructions leveraged the ∼7-14° angular separation between slots to achieve median TRE ∼2 mm and <2° from a single scan. CONCLUSION: The multi-slot configuration provided intraoperative visualization of long spine segments, facilitating target localization, assessment of global spinal alignment, and evaluation of long surgical constructs. 3D-2D registration to long-length tomosynthesis reconstructions yielded a promising means of guidance and verification with accuracy exceeding that of 3D-2D registration to conventional radiographs.

Spinal Navigation and Imaging: History, Trends, and Future.

The clinical practice of spine navigation has rapidly grown with the development of image-based guidance. In this paper, a brief history of spinal navigation is presented and a review of clinical outcomes for 12,622 pedicle screws placed using the latest technology in the sacral, lumbar and thoracic regions. The clinical evidence demonstrate that intraoperative 3D image guided surgery has a 96.8% success rate. A concluding section detailing existing barriers that limit more widespread adoption and future development efforts is presented.

Wall-motion based analysis of global and regional left atrial mechanics.

Atrial fibrillation is an increasingly prevalent cardiovascular disease; changes in atrial structure and function induced by atrial fibrillation and its treatments are often spatially heterogeneous. However, spatial heterogeneity of function is difficult to assess with standard imaging techniques. This paper describes a method to assess global and regional mechanical function by combining cardiac magnetic resonance imaging and finite-element surface fitting. We used this fitted surface to derive measures of left atrial volume, regional motion, and spatial heterogeneity of motion in 23 subjects, including healthy volunteers and atrial fibrillation patients. We fit the surfaces using a Newton optimization scheme in under 1 min on a standard laptop, with a root mean square error of 2.3 ± 0.5 mm, less than 9% of the mean fitted radius, and an inter-operator variability of less than 10%. Fitted surfaces showed clear definition of the phases of left atrial motion (filling, passive emptying, active contraction) in both volume-time and regional radius-time curves. Averaged surfaces of healthy volunteers and atrial fibrillation patients provided evidence of substantial regional variation in both amount and timing of regional motion, indicating spatial heterogeneity of function, even in healthy adults.

Serial ultrasound evaluation of intramyocardial strain after reperfused myocardial infarction reveals that remote zone dyssynchrony develops in concert with left ventricular remodeling.

This study noninvasively evaluated the development of left ventricular (LV) dyssynchrony following reperfused myocardial infarction (MI) in mice using an ultrasonic speckle-tracking method. Eight C57BL/6J mice were assessed by high-resolution echocardiography at baseline and at eight time-points following MI. Images were acquired at 1mm elevational intervals encompassing the entire LV to determine chamber volumes and radial strain. Receiver-operating characteristic (ROC) analysis of regional radial strain was used to segment the three-dimensional (3-D) LV into infarct, adjacent and remote zones. This in vivo segmentation was correlated to histologic infarct size (R = 0.89, p < 0.01) in a short-axis, slice-by-slice comparison. The onset of dyssynchrony during LV remodeling was assessed by standard deviation of time to peak radial strain in the infarct, adjacent and remote zones. It was discovered that the form of LV dyssynchrony that develops in the remote zone late after MI does so in concert with the progression of LV remodeling (R = 0.70, p < 0.05).

Balanced multipoint displacement encoding for DENSE MRI.

Displacement encoding with stimulated echoes (DENSE) is a quantitative imaging technique that encodes tissue displacement in the phase of the acquired signal. Various DENSE sequences have encoded displacement using methods analogous to the simple multipoint methods of phase contrast (PC) MRI. We developed general n-dimension balanced multipoint encoding for DENSE. Using these methods, phase noise variance decreased experimentally by 73.7%, 65.6%, and 61.9% compared with simple methods, which closely matched the theoretical decreases of 75%, 66.7%, and 62.5% for one-dimensional (1D), 2D, and 3D encoding, respectively. Phase noise covariances decreased by 99.2% and 99.3% for balanced 2D and 3D encoding, consistent with the zero-covariance prediction. The direction bias inherent to the simple methods was decreased to almost zero using balanced methods. Reduced phase noise and improved displacement and strain maps using balanced methods were visually observed in phantom and volunteer images. Balanced multipoint encoding can also be applied to PC MRI.

Postinfarction myocardial scarring in mice: molecular MR imaging with use of a collagen-targeting contrast agent.

PURPOSE: To prospectively evaluate a gadolinium-based collagen-targeting contrast agent, EP-3533, for in vivo magnetic resonance (MR) imaging of myocardial fibrosis in a mouse model of healed myocardial infarction (MI). MATERIALS AND METHODS: All procedures were performed in accordance with protocols approved by the animal care and use committee. MI was induced in eight mice by means of occlusion of the left anterior descending coronary artery followed by reperfusion. Four MR examinations were performed in each animal: one examination before, one examination 1 day after, and two examinations 6 weeks after the MI. For the latter two examinations, electrocardiographically gated inversion-recovery gradient-echo MR images were acquired before and serially (every 5 minutes) after the intravenous injection of either gadopentetate dimeglumine or EP-3533. The image enhancement kinetic properties of the postinfarction scar, normal myocardium, and blood were compared. RESULTS: Dynamic T1-weighted MR imaging revealed the washout time constants for EP-3533 to be significantly longer than those for gadopentetate dimeglumine in regions of postinfarction scarring (mean, 194.8 minutes +/-116.8 [standard deviation] vs 25.5 minutes +/- 4.2; P < .05) and in normal myocardium (mean, 45.4 minutes +/- 16.7 vs 25.1 minutes +/- 9.7; P < .05). Findings on postmortem histologic sections stained for collagen correlated well with EP-3533-enhanced areas seen on inversion-recovery MR images. Fifty minutes after EP-3533 injection, the postinfarction scar tissue samples, as compared with the normal myocardium, had a twofold higher concentration of gadolinium. CONCLUSION: Use of the gadolinium-based collagen-targeting contrast agent, EP-3533, enabled in vivo molecular MR imaging of fibrosis in a mouse model of healed postinfarction myocardial scarring.

Imaging two-dimensional displacements and strains in skeletal muscle during joint motion by cine DENSE MR.

The objective of this study was to apply cine magnetic resonance imaging (MRI) using displacement encoding with stimulated echoes (DENSE) to measure the dynamic two-dimensional (2D) displacement and Lagrangian strain fields in the biceps brachii muscle. Six healthy volunteers underwent cine DENSE MRI during repeated elbow flexion against the load of gravity. Displacement encoded dynamic images of the upper arm were acquired with spatial and temporal resolutions of 1.9 x 1.9 mm(2) and 30 ms, respectively. Pixel-wise Lagrangian displacement and strain fields were calculated from the measured images. We extracted the first and second principal strains (E1 and E2) along the centerline and anterior regions of the muscle. E1 and E2 were relatively uniform along the anterior region. However, E1 and E2 were both non-uniform along the centerline region-normalized values for E1 and E2 varied over the ranges of 0.27-1.35, and 0.45-2.36, respectively. The directions of the first and second principal strains varied throughout the muscle and showed that the direction of principal shortening is not necessarily aligned with fascicle direction. This study demonstrates the utility of cine DENSE MRI for analyzing skeletal muscle mechanics and provides data describing the in vivo mechanics of muscle tissue to a level of detail that has not been previously possible.

Multi-parameter in vivo cardiac magnetic resonance imaging demonstrates normal perfusion reserve despite severely attenuated beta-adrenergic functional response in neuronal nitric oxide synthase knockout mice.

AIMS: The role of neuronal nitric oxide synthase (nNOS) in regulating contractile function remains controversial, and in regulating myocardial perfusion is uninvestigated. We used magnetic resonance imaging (MRI) to phenotype nNOS(-/-) and wild-type (WT) mice regarding left ventricular (LV) structure, baseline function, beta-adrenergic responsiveness, and perfusion reserve. METHODS AND RESULTS: Cine MRI showed higher LV mass to end-diastolic volume ratio (2.3 +/- 0.2 mg/microL nNOS(-/-) vs. 1.7 +/- 0.1 mg/microL WT; P=0.032) and LV ejection fraction (64.9 +/- 2.1% nNOS(-/-) vs. 55.8 +/- 1.1% WT; P = 0.003) in nNOS(-/-). Myocardial tagging demonstrated similar baseline systolic circumferential strain (Ecc) in nNOS(-/-) and WT. With dobutamine, the normal change in Ecc was nearly absent in nNOS(-/-) (-0.5 +/- 0.3% nNOS(-/-) vs. -2.2 +/- 0.3% WT; P = 0.001), and the systolic strain rate (dEcc/dt) response to dobutamine seen in WT was reduced in nNOS(-/-) (-29 +/- 13%/s nNOS(-/-) vs. -106+/-16%/s WT; P = 0.001). Diastolic strain rate increased significantly with dobutamine only in WT. Arterial spin labelling showed that baseline perfusion and perfusion reserve with either dobutamine or an adenosine receptor agonist are normal in nNOS(-/-). CONCLUSION: MRI provides non-invasive in vivo evidence that nNOS does not play a role in basal contractile function or myocardial perfusion, but is required for increasing cardiac inotropy and lusitropy upon beta-adrenergic stimulation.

Three-dimensional mapping of optimal left ventricular pacing site for cardiac resynchronization.

BACKGROUND: The efficacy of cardiac resynchronization therapy (CRT) depends on placement of the left ventricular lead within the late-activated territory. The geographic extent and 3-dimensional distribution of left ventricular (LV) locations yielding optimal CRT remain unknown. METHODS AND RESULTS: Normal or tachypacing-induced failing canine hearts made dyssynchronous by right ventricular free wall pacing or chronic left bundle-branch ablation were acutely instrumented with a nonconstraining epicardial elastic sock containing 128 electrodes interfaced with a computer-controlled stimulation/recording system. Biventricular CRT was performed using a fixed right ventricular site and randomly selected LV sites covering the entire free wall. For each LV site, global cardiac function (conductance catheter) and mechanical synchrony (magnetic resonance imaging tagging) were determined to yield 3-dimensional maps reflecting CRT impact. Optimal CRT was achieved from LV lateral wall sites, slightly more anterior than posterior and more apical than basal. LV sites yielding > or = 70% of the maximal dP/dtmax increase covered approximately 43% of the LV free wall. This distribution and size were similar in both normal and failing hearts. The region was similar for various systolic and diastolic parameters and correlated with 3-dimensional maps based on mechanical synchrony from magnetic resonance imaging strain analysis. CONCLUSIONS: In hearts with delayed lateral contraction, optimized CRT is achieved over a fairly broad area of LV lateral wall in both nonfailing and failing hearts, with modest anterior or posterior deviation still capable of providing effective CRT. Sites selected to achieve the most mechanical synchrony are generally similar to those that most improve global function, confirming a key assumption underlying the use of wall motion analysis to optimize CRT.

Evidence of structural remodeling in the dyssynchronous failing heart.

Ventricular remodeling of both geometry and fiber structure is a prominent feature of several cardiac pathologies. Advances in MRI and analytical methods now make it possible to measure changes of cardiac geometry, fiber, and sheet orientation at high spatial resolution. In this report, we use diffusion tensor imaging to measure the geometry, fiber, and sheet architecture of eight normal and five dyssynchronous failing canine hearts, which were explanted and fixed in an unloaded state. We apply novel computational methods to identify statistically significant changes of cardiac anatomic structure in the failing and control heart populations. The results demonstrate significant regional differences in geometric remodeling in the dyssynchronous failing heart versus control. Ventricular chamber dilatation and reduction in wall thickness in septal and some posterior and anterior regions are observed. Primary fiber orientation showed no significant change. However, this result coupled with the local wall thinning in the septum implies an altered transmural fiber gradient. Further, we observe that orientation of laminar sheets become more vertical in the early-activated septum, with no significant change of sheet orientation in the late-activated lateral wall. Measured changes in both fiber gradient and sheet structure will affect both the heterogeneity of passive myocardial properties as well as electrical activation of the ventricles.

Ex vivo 3D diffusion tensor imaging and quantification of cardiac laminar structure.

A three-dimensional (3D) diffusion-weighted imaging (DWI) method for measuring cardiac fiber structure at high spatial resolution is presented. The method was applied to the ex vivo reconstruction of the fiber architecture of seven canine hearts. A novel hypothesis-testing method was developed and used to show that distinct populations of secondary and tertiary eigenvalues may be distinguished at reasonable confidence levels (P < or = 0.01) within the canine ventricle. Fiber inclination and sheet angles are reported as a function of transmural depth through the anterior, lateral, and posterior left ventricle (LV) free wall. Within anisotropic regions, two consistent and dominant orientations were identified, supporting published results from histological studies and providing strong evidence that the tertiary eigenvector of the diffusion tensor (DT) defines the sheet normal.

Visualization of tensor fields using superquadric glyphs.

The spatially varying tensor fields that arise in magnetic resonance imaging are difficult to visualize due to the multivariate nature of the data. To improve the understanding of myocardial structure and function a family of objects called glyphs, derived from superquadric parametric functions, are used to create informative and intuitive visualizations of the tensor fields. The superquadric glyphs are used to visualize both diffusion and strain tensors obtained in canine myocardium. The eigensystem of each tensor defines the glyph shape and orientation. Superquadric functions provide a continuum of shapes across four distinct eigensystems (lambda(i), sorted eigenvalues), lambda(1) = lambda(2) = lambda(3) (spherical), lambda(1) < lambda(2) = lambda(3) (oblate), lambda(1) > lambda(2) = lambda(3) (prolate), and lambda(1) > lambda(2) > lambda(3) (cuboid). The superquadric glyphs are especially useful for identifying regions of anisotropic structure and function. Diffusion tensor renderings exhibit fiber angle trends and orthotropy (three distinct eigenvalues). Visualization of strain tensors with superquadric glyphs compactly exhibits radial thickening gradients, circumferential and longitudinal shortening, and torsion combined. The orthotropic nature of many biologic tissues and their DTMRI and strain data require visualization strategies that clearly exhibit the anisotropy of the data if it is to be interpreted properly. Superquadric glyphs improve the ability to distinguish fiber orientation and tissue orthotropy compared to ellipsoids.