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.

Whole-lesion assessment of volume and signal changes after sclerotherapy of extremity venous malformations.

PURPOSE: To investigate quantitative changes in MRI signal intensity (SI) and lesion volume that indicate treatment response and correlate these changes with clinical outcomes after percutaneous sclerotherapy (PS) of extremity venous malformations (VMs). METHODS: VMs were segmented manually on pre- and post-treatment T2-weighted MRI using 3D Slicer to assess changes in lesion volume and SI. Clinical outcomes were scored on a 7-point Likert scale according to patient perception of symptom improvement; treatment response (success or failure) was determined accordingly. RESULTS: Eighty-one patients with VMs underwent 125 PS sessions. Treatment success occurred in 77 patients (95 %). Mean (±SD) changes were -7.9 ± 24 cm3 in lesion volume and -123 ± 162 in SI (both, P <.001). Mean reduction in lesion volume was greater in the success group (-9.4 ± 24 cm3) than in the failure group (21 ± 20 cm3) (P =.006). Overall, lesion volume correlated with treatment response (ρ = -0.3, P =.004). On subgroup analysis, volume change correlated with clinical outcomes in children (ρ = -0.3, P =.03), in sodium tetradecyl sulfate-treated lesions (ρ = -0.5, P =.02), and in foot lesions (ρ = -0.6, P =.04). SI change correlated with clinical outcomes in VMs treated in 1 PS session (ρ = -0.3, P =.01) and in bleomycin-treated lesions (ρ = -0.4, P =.04). CONCLUSIONS: Change in lesion volume is a reliable indicator of treatment response. Lesion volume and SI correlate with clinical outcomes in specific subgroups.

Automated identification of fleck lesions in Stargardt disease using deep learning enhances lesion detection sensitivity and enables morphometric analysis of flecks.

PURPOSE: To classify fleck lesions and assess artificial intelligence (AI) in identifying flecks in Stargardt disease (STGD). METHODS: A retrospective study of 170 eyes from 85 consecutive patients with confirmed STGD. Fundus autofluorescence images were extracted, and flecks were manually outlined. A deep learning model was trained, and a hold-out testing subset was used to compare with manually identified flecks and for graders to assess. Flecks were clustered using K-means clustering. RESULTS: Of the 85 subjects, 45 were female, and the median age was 37 years (IQR 25-59). A subset of subjects (n=41) had clearly identifiable fleck lesions, and an AI was successfully trained to identify these lesions (average Dice score of 0.53, n=18). The AI segmentation had smaller (0.018 compared with 0.034 mm2, p<0.001) but more numerous flecks (75.5 per retina compared with 40.0, p<0.001), but the total size of flecks was not different. The AI model had higher sensitivity to detect flecks but resulted in more false positives. There were two clusters of flecks based on morphology: broadly, one cluster of small round flecks and another of large amorphous flecks. The per cent frequency of small round flecks negatively correlated with subject age (r=-0.31, p<0.005). CONCLUSIONS: AI-based detection of flecks shows greater sensitivity than human graders but with a higher false-positive rate. With further optimisation to address current shortcomings, this approach could be used to prescreen subjects for clinical research. The feasibility and utility of quantifying fleck morphology in conjunction with AI-based segmentation as a biomarker of progression require further study.

Comparative analysis of alignment algorithms for macular optical coherence tomography imaging.

BACKGROUND: Optical coherence tomography (OCT) is the most important and commonly utilized imaging modality in ophthalmology and is especially crucial for the diagnosis and management of macular diseases. Each OCT volume is typically only available as a series of cross-sectional images (B-scans) that are accessible through proprietary software programs which accompany the OCT machines. To maximize the potential of OCT imaging for machine learning purposes, each OCT image should be analyzed en bloc as a 3D volume, which requires aligning all the cross-sectional images within a particular volume. METHODS: A dataset of OCT B-scans obtained from 48 age-related macular degeneration (AMD) patients and 50 normal controls was used to evaluate five registration algorithms. After alignment of B-scans from each patient, an en face surface map was created to measure the registration quality, based on an automatically generated Laplace difference of the surface map-the smoother the surface map, the smaller the average Laplace difference. To demonstrate the usefulness of B-scan alignment, we trained a 3D convolutional neural network (CNN) to detect age-related macular degeneration (AMD) on OCT images and compared the performance of the model with and without B-scan alignment. RESULTS: The mean Laplace difference of the surface map before registration was 27 ± 4.2 pixels for the AMD group and 26.6 ± 4 pixels for the control group. After alignment, the smoothness of the surface map was improved, with a mean Laplace difference of 5.5 ± 2.7 pixels for Advanced Normalization Tools Symmetric image Normalization (ANTs-SyN) registration algorithm in the AMD group and a mean Laplace difference of 4.3 ± 1.4.2 pixels for ANTs in the control group. Our 3D CNN achieved superior performance in detecting AMD, when aligned OCT B-scans were used (AUC 0.95 aligned vs. 0.89 unaligned). CONCLUSIONS: We introduced a novel metric to quantify OCT B-scan alignment and compared the effectiveness of five alignment algorithms. We confirmed that alignment could be improved in a statistically significant manner with readily available alignment algorithms that are available to the public, and the ANTs algorithm provided the most robust performance overall. We further demonstrated that alignment of OCT B-scans will likely be useful for training 3D CNN models.

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.

Interrater Reliability of Cervical Neural Foraminal Stenosis Using Traditional and Splayed Reconstructions: Analysis of One Hundred Scans.

OBJECTIVE: The oblique sagittal orientation of the cervical neural foramina hinders the evaluation of cervical neural foraminal stenosis (CNFS) on traditional axial and sagittal slices. Traditional image reconstruction techniques to generate oblique slices provide only a view of the foramina unilaterally. We present a simple technique for generating splayed slices that show the bilateral neuroforamina simultaneously and assess its reliability compared with traditional axial windows. METHODS: Cervical computed tomography (CT) scans from 100 patients were retrospectively collected and de-identified. The axial slices were reformatted into a curved reformat with the plane of the reformat extending across the bilateral neuroforamina. The foramina along the C2-T1 vertebral levels were assessed by 4 neuroradiologists using the axial and splayed slices. The intrarater agreement across the axial and splayed slices for a given foramen and the interrater agreement for the axial and splayed slices individually were calculated using the Cohen κ statistic. RESULTS: Interrater agreement was overall higher for the splayed slices (κ = 0.25) compared with the axial slices (κ = 0.20). The splayed slices were more likely to have fair agreement across raters compared with the axial slices. Intrarater agreement between the axial and splayed slices was poorer for residents compared with fellows. CONCLUSIONS: Splayed reconstructions showing the bilateral neuroforamina en face can be readily generated from axial CT imaging. These splayed reconstructions can improve the consistency of CNFS evaluation compared with traditional CT slices and should be considered in the workup of CNFS, particularly for less experienced readers.

Prediction of visual impairment in retinitis pigmentosa using deep learning and multimodal fundus images.

BACKGROUND: The efficiency of clinical trials for retinitis pigmentosa (RP) treatment is limited by the screening burden and lack of reliable surrogate markers for functional end points. Automated methods to determine visual acuity (VA) may help address these challenges. We aimed to determine if VA could be estimated using confocal scanning laser ophthalmoscopy (cSLO) imaging and deep learning (DL). METHODS: Snellen corrected VA and cSLO imaging were obtained retrospectively. The Johns Hopkins University (JHU) dataset was used for 10-fold cross-validations and internal testing. The Amsterdam University Medical Centers (AUMC) dataset was used for external independent testing. Both datasets had the same exclusion criteria: visually significant media opacities and images not centred on the central macula. The JHU dataset included patients with RP with and without molecular confirmation. The AUMC dataset only included molecularly confirmed patients with RP. Using transfer learning, three versions of the ResNet-152 neural network were trained: infrared (IR), optical coherence tomography (OCT) and combined image (CI). RESULTS: In internal testing (JHU dataset, 2569 images, 462 eyes, 231 patients), the area under the curve (AUC) for the binary classification task of distinguishing between Snellen VA 20/40 or better and worse than Snellen VA 20/40 was 0.83, 0.87 and 0.85 for IR, OCT and CI, respectively. In external testing (AUMC dataset, 349 images, 166 eyes, 83 patients), the AUC was 0.78, 0.87 and 0.85 for IR, OCT and CI, respectively. CONCLUSIONS: Our algorithm showed robust performance in predicting visual impairment in patients with RP, thus providing proof-of-concept for predicting structure-function correlation based solely on cSLO imaging in patients with RP.

Active shape model registration of ocular structures in computed tomography images.

Purpose. The goal of this work is to create an active shape model segmentation method based on the statistical shape model of five regions of the globe on computed tomography (CT) scans and to use the method to categorize normal globe from globe injury.Methods. A set of 78 normal globes imaged with CT scans were manually segmented (vitreous cavity, lens, sclera, anterior chamber, and cornea) by two graders. A statistical shape model was created from the regions. An active shape model was trained using the manual segmentations and the statistical shape model and was assessed using leave-one-out cross validations. The active shape model was then applied to a set of globes with open globe injures, and the segmentations were compared to those of normal globes, in terms of the standard deviations away from normal.Results. The active shape model (ASM) segmentation compared well to ground truth, based on Dice similarity coefficient score in a leave-one-out experiment: 90.2% ± 2.1% for the cornea, 92.5% ± 3.5% for the sclera, 87.4% ± 3.7% for the vitreous cavity, 83.5% ± 2.3% for the anterior chamber, and 91.2% ± 2.4% for the lens. A preliminary set of CT scans of patients with open globe injury were segmented using the ASM and the shape of each region was quantified. The sclera and vitreous cavity were statistically different in shape from the normal. The Zone 1 and Zone 2 globes were statistically different than normal from the cornea and anterior chamber. Both results are consistent with the definition of the zonal injuries in OGI.Conclusion. The ASM results were found to be reproducible and accurately correlated with manual segmentations. The quantitative metrics derived from ASM of globes with OGI are consistent with existing medical knowledge in terms of structural deformation.

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.

Direct quantification of epistemic and aleatoric uncertainty in 3D U-net segmentation.

Purpose: To derive a multinomial probability function and quantitative measures of the data and epistemic uncertainty as direct output of a 3D U-Net segmentation network. Approach: A set of T1 brain MRI images were downloaded from the Connectome Project and segmented using FMRIB's FAST algorithm to be used as ground truth. A 3D U-Net neural network was trained with sample sizes of 200, 500, and 898 T1 brain images using a loss function defined as the negative logarithm of the likelihood based on a derivation of the definition of the multinomial probability function. From this definition, the epistemic and aleatoric uncertainty equations were derived and used to quantify maps of the uncertainty along with tissue segmentations. Results: Maps of the tissue segmentation along with the epistemic and aleatoric uncertainty, per voxel, are presented. The uncertainty decreased based on the increasing number of training data used to train the neural network. The neural network trained with 898 volumes resulted in uncertainty maps that were high primarily in the tissue boundary regions. The epistemic and aleatoric uncertainty were averaged over all test data (connectome and tumor separately), and the epistemic uncertainty showed a decreasing trend, as expected, with increasing numbers of data used to train the model. The aleatoric uncertainty showed a similar trend which was also expected as the aleatoric uncertainty is not expected to be as dependent on the number of training data. Conclusion: The derived uncertainty equations from a multinomial probability distribution were able to quantify the aleatoric and epistemic uncertainty per voxel and are applicable for all two-dimensional and three-dimensional neural networks.

Automated prediction of the Thoracolumbar Injury Classification and Severity Score from CT using a novel deep learning algorithm.

OBJECTIVE: Damage to the thoracolumbar spine can confer significant morbidity and mortality. The Thoracolumbar Injury Classification and Severity Score (TLICS) is used to categorize injuries and determine patients at risk of spinal instability for whom surgical intervention is warranted. However, calculating this score can constitute a bottleneck in triaging and treating patients, as it relies on multiple imaging studies and a neurological examination. Therefore, the authors sought to develop and validate a deep learning model that can automatically categorize vertebral morphology and determine posterior ligamentous complex (PLC) integrity, two critical features of TLICS, using only CT scans. METHODS: All patients who underwent neurosurgical consultation for traumatic spine injury or degenerative pathology resulting in spine injury at a single tertiary center from January 2018 to December 2019 were retrospectively evaluated for inclusion. The morphology of injury and integrity of the PLC were categorized on CT scans. A state-of-the-art object detection region-based convolutional neural network (R-CNN), Faster R-CNN, was leveraged to predict both vertebral locations and the corresponding TLICS. The network was trained with patient CT scans, manually labeled vertebral bounding boxes, TLICS morphology, and PLC annotations, thus allowing the model to output the location of vertebrae, categorize their morphology, and determine the status of PLC integrity. RESULTS: A total of 111 patients were included (mean ± SD age 62 ± 20 years) with a total of 129 separate injury classifications. Vertebral localization and PLC integrity classification achieved Dice scores of 0.92 and 0.88, respectively. Binary classification between noninjured and injured morphological scores demonstrated 95.1% accuracy. TLICS morphology accuracy, the true positive rate, and positive injury mismatch classification rate were 86.3%, 76.2%, and 22.7%, respectively. Classification accuracy between no injury and suspected PLC injury was 86.8%, while true positive, false negative, and false positive rates were 90.0%, 10.0%, and 21.8%, respectively. CONCLUSIONS: In this study, the authors demonstrate a novel deep learning method to automatically predict injury morphology and PLC disruption with high accuracy. This model may streamline and improve diagnostic decision support for patients with thoracolumbar spinal trauma.

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.

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.

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.

Measurement of arteriolar blood volume in brain tumors using MRI without exogenous contrast agent administration at 7T.

PURPOSE: Arteriolar cerebral-blood-volume (CBVa) is an important perfusion parameter that can be measured using inflow-based vascular-space-occupancy (iVASO) MRI without exogenous contrast agent administration. The purpose of this study is to assess the potential diagnostic value of CBVa in brain tumor patients by comparing it with total-CBV (including arterial, capillary and venous vessels) measured by dynamic-susceptibility-contrast (DSC) MRI. MATERIALS AND METHODS: Twelve brain tumor patients were scanned using iVASO (on 7T as part of a research project) and DSC (on 3T as part of routine clinical protocols) MRI. Region-of-interest analysis was performed to compare the resulting perfusion measures between tumoral and contralateral regions, and to evaluate their associations with tumor grades. RESULTS: CBVa measured by iVASO MRI significantly correlated with WHO grade (ρ = 0.37, P = 0.04). Total-CBV measured by DSC MRI showed a trend of correlation with WHO grade (ρ = 0.28, P = 0.5). The signal-to-noise ratio was comparable (P > 0.1) between the two methods, while the contrast-to-noise ratio between tumoral and contralateral regions was higher in iVASO-CBVa than DSC-CBV in WHO II/III patients (P < 0.05) but comparable in WHO IV patients (P > 0.1). A trend of positive correlation between DSC-CBV and iVASO-CBVa was observed (R2 = 0.28, P = 0.07). CONCLUSION: In this initial patient study, CBVa demonstrated a stronger correlation with WHO grade than total-CBV. Further investigation with a larger cohort is warranted to validate whether CBVa can be a better classifier than total-CBV for the stratification of brain tumors, and whether iVASO MRI can be a useful alternative method for the assessment of tumor perfusion, especially when exogenous contrast agent administration is difficult in certain patient populations. J. Magn. Reson. Imaging 2016;44:1244-1255.

Demonstration of Brain Tumor-Induced Neurovascular Uncoupling in Resting-State fMRI at Ultrahigh Field.

To demonstrate in a small case series for the first time the phenomenon of brain tumor-related neurovascular uncoupling (NVU) in resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at ultrahigh field (7T). Two de novo (i.e., untreated) brain tumor patients underwent both BOLD resting-state fMRI (rsfMRI) on a 7T MRI system and motor task-based BOLD fMRI at 3T. Ipsilesional (i.e., ipsilateral to tumor or IL) and contralesional (i.e., contralateral to tumor or CL) region of interest (ROI) analysis was performed on both 3T motor task-related general linear model-derived activation maps and on 7T rsfMRI independent component analysis (ICA)-derived sensorimotor network maps for each case. Asymmetry scores (ASs) were computed based on numbers of suprathreshold voxels in the IL and CL ROIs. In each patient, ASs derived from ROI analysis of suprathreshold voxels in IL and CL ROIs in task-related activation maps and rsfMRI ICA-derived sensorimotor component maps indicate greater number of suprathreshold voxels in contralesional than ipsilesional sensorimotor cortex in both maps. In patient 1, an AS of 0.2 was obtained from the suprathreshold Z-score spectrum (voxels with Z-scores >5.0) of the task-based activation map and AS of 1.0 was obtained from the suprathreshold Z-score spectrum (Z-scores >5.0) of the ICA-derived sensorimotor component map. Similarly, in patient 2, an AS of 1.0 was obtained from the suprathreshold Z-score spectrum (Z-scores >5.0) of the task-based activation map and an AS of 1.0 was obtained from the suprathreshold Z-score spectrum (Z-scores >5.0) of the ICA-derived sensorimotor component map. Overall, decreased BOLD signal was noted in IL compared with CL ROIs on both task-based activation maps and ultrahigh field resting-state maps, indicating the presence of NVU. We have demonstrated evidence of NVU on ultrahigh field 7T rsfMRI comparable with the findings on standard 3T motor task-based fMRI in both cases.

Magnetization transfer contrast-suppressed imaging of amide proton transfer and relayed nuclear overhauser enhancement chemical exchange saturation transfer effects in the human brain at 7T.

PURPOSE: To use the variable delay multipulse (VDMP) chemical exchange saturation transfer (CEST) approach to obtain clean amide proton transfer (APT) and relayed Nuclear Overhauser enhancement (rNOE) CEST images in the human brain by suppressing the conventional magnetization transfer contrast (MTC) and reducing the direct water saturation contribution. METHODS: The VDMP CEST scheme consists of a train of RF pulses with a specific mixing time. The CEST signal with respect to the mixing time shows distinguishable characteristics for protons with different exchange rates. Exchange rate filtered CEST images are generated by subtracting images acquired at two mixing times at which the MTC signals are equal, while the APT and rNOE-CEST signals differ. Because the subtraction is performed at the same frequency offset for each voxel and the CEST signals are broad, no B0 correction is needed. RESULTS: MTC-suppressed APT and rNOE-CEST images of human brain were obtained using the VDMP method. The APT-CEST data show hyperintensity in gray matter versus white matter, whereas the rNOE-CEST images show negligible contrast between gray and white matter. CONCLUSION: The VDMP approach provides a simple and rapid way of recording MTC-suppressed APT-CEST and rNOE-CEST images without the need for B0 field correction.

Magnetic susceptibility contrast variations in multiple sclerosis lesions.

PURPOSE: Recent magnetic resonance imaging (MRI) studies have revealed heterogeneous magnetic susceptibility contrasts in multiple sclerosis (MS) lesions. Due to its sensitivity to disease-related iron and myelin changes, magnetic susceptibility-based measures may better reflect some pathological features of MS lesions. Hence, we sought to characterize MS lesions using combined R2* mapping and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: In all, 306 MS lesions were selected from 24 MS patients who underwent 7T MRI. Maps of R2*, frequency, and quantitative susceptibility were calculated using acquired multiecho gradient echo (GRE) phase data. Lesions were categorized based on their image intensity or their anatomical locations. R2* and susceptibility values were quantified in each lesion based on manually drawn lesion masks and compared between lesion groups showing different contrast patterns. Correlations between R2* and susceptibility were also tested in these lesion groups. RESULTS: In 38% of selected lesions the frequency map did not show the same contrast pattern as the susceptibility map. While most lesions (93%) showed hypointensity on R2*, the susceptibility contrast in lesions varied, with 40% being isointense and 58% being hyperintense in the lesion core. Significant correlations (r = 0.31, P < 0.001) between R2* and susceptibility were found in susceptibility hyperintense lesions, but not in susceptibility isointense lesions. In addition, a higher proportion (74%) of periventricular lesions was found to be susceptibility hyperintense as compared to subcortical (53%) or juxtacortical (38%) lesions. CONCLUSION: Combining R2* and QSM is useful to characterize heterogeneity in MS lesions.

Whole-brain amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging in glioma patients using low-power steady-state pulsed chemical exchange saturation transfer (CEST) imaging at 7T.

PURPOSE: To explore the relationship of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signal intensities with respect to different World Health Organization (WHO) brain tumor grades (II to IV) at 7T. MATERIALS AND METHODS: APT-based and NOE-based signals at 7T using low-power steady-state chemical exchange saturation transfer (CEST) were compared among de novo primary gliomas of different WHO grades (II to IV). The quantitative APT and NOE signals, calculated by fitting approach using extrapolated semisolid MT reference (EMR) signals, were compared with the magnetization transfer ratio asymmetry (MTRasym ) analysis, commonly used in APT-weighted MRI. RESULTS: The observed NOE signals of all glioma grades were significantly lower than normal brain tissue (P < 0.01). NOE signals significantly differed between low-grade (II) gliomas and high-grade (III, IV) gliomas (P < 0.05). APT signals showed no difference between the tumor regions for any glioma grades (M = 3.08%, 2.64%, and 3.10%, 95% confidence interval [CI] = 2.81% ∼ 3.33%, 2.36% ∼ 2.91%, and 2.85% ∼ 3.36% for grade II, III, and IV, respectively), and between normal brain tissue and all glioma grades (P = 0.08, M = 4.29% and 2.94%, 95% CI = 3.57% ∼ 4.99% and 2.47% ∼ 3.41% for normal and average grade II, III, and IV), while MTRasym differed significantly between normal tissue and all glioma grades (P < 0.05). CONCLUSION: NOE contributes substantially to APT-weighted MRI at 7T at low RF saturation power and provides a promising biomarker for glioma grading.J. Magn. Reson. Imaging 2016;44:41-50.

Reproducibility and Temporal Structure in Weekly Resting-State fMRI over a Period of 3.5 Years.

Resting-state functional MRI (rs-fMRI) permits study of the brain's functional networks without requiring participants to perform tasks. Robust changes in such resting state networks (RSNs) have been observed in neurologic disorders, and rs-fMRI outcome measures are candidate biomarkers for monitoring clinical trials, including trials of extended therapeutic interventions for rehabilitation of patients with chronic conditions. In this study, we aim to present a unique longitudinal dataset reporting on a healthy adult subject scanned weekly over 3.5 years and identify rs-fMRI outcome measures appropriate for clinical trials. Accordingly, we assessed the reproducibility, and characterized the temporal structure of, rs-fMRI outcome measures derived using independent component analysis (ICA). Data was compared to a 21-person dataset acquired on the same scanner in order to confirm that the values of the single-subject RSN measures were within the expected range as assessed from the multi-participant dataset. Fourteen RSNs were identified, and the inter-session reproducibility of outcome measures-network spatial map, temporal signal fluctuation magnitude, and between-network connectivity (BNC)-was high, with executive RSNs showing the highest reproducibility. Analysis of the weekly outcome measures also showed that many rs-fMRI outcome measures had a significant linear trend, annual periodicity, and persistence. Such temporal structure was most prominent in spatial map similarity, and least prominent in BNC. High reproducibility supports the candidacy of rs-fMRI outcome measures as biomarkers, but the presence of significant temporal structure needs to be taken into account when such outcome measures are considered as biomarkers for rehabilitation-style therapeutic interventions in chronic conditions.