The design philosophy of leading interventional devices and software typically employs point- or line-like fiducial markers that are detected via multiple external optical cameras and/or the primary medical imaging system employed in the procedure (MRI, CT, fluoroscopy, etc.). Fiducial markers with characteristic geometric signals encoded into their physical design can provide more robust information on device location and orientation than point or line signals at lower imaging resolutions while leveraging the volumetric imaging capabilities of MRI and CT to circumvent the need for additional external camera hardware in the operating room. This work describes efforts to develop unique geometric fiducial designs and software methods to detect and determine their orientation based on volumetric MR-imaging. Using these methods, a single MR scan can be used to localize and orient specific medical devices autonomously, rather than relying on multimodal imaging or semi-manual detection methods. These results have been validated in a series of MRI scans using human cadaver heads and fruit-based phantoms, successfully detecting and isolating the device fiducial in 8/8 T2w MRI scans, and coregistering the signal to an orthonormal template with a Dice-based evaluation metric of 0.819. These methods have the potential to accelerate imageguided surgeries by improving automated detection and registration methods to reduce the number and/or duration of required scans while minimizing the amount of supplemental hardware (external optical cameras).

Background:Magnetic resonance imaging (MRI) guided, minimally invasive transperineal interventions have been shown to produce positive clinical outcomes, specifically regarding prostate biopsy and cryoablation of prostate cancer. Many vendors, however, do not provide guidance to clinicians as to how their devices, biopsy needles and cryoprobes should be inserted during procedures. As a result, many leading research institutions have developed in-house solutions for needle insertion guidance. Institutions with less research and engineering support may find the development of their own in-house solutions infeasible, leading to a gap in clinical practice. Our purpose was to develop a replicable toolset using minimal hardware and software to facilitate MRI-guided prostate biopsy and cryoablation. The toolset was validated first in a series of phantom trials, then in a clinical cohort of 24 patients from a single institution. Methods:This study utilized a grid-like rigid trajectory guide coupled with custom software to simulate in phantoms, and then perform on patients, prostate-focused interventional procedures using a closed bore General Electric 450W scanner. Only standard imaging sequences were employed, allowing this work to be generalizable between different scanners with no additional setup. Interventionalists imported the coordinates of the targets in the prostate and the 3 saline-filled fiducial markers on the grid into custom software, which then identified the grid hole and depth of insertion necessary to drive needles to the targeted points. In phantom trials, the targeting error of each insertion was logged. All patients enrolled in the study were men over the age of 50 years with either biopsy-confirmed prostate cancer with magnetic resonance (MR)-visible lesions or prostatic fluid collection. Each patient was reviewed by a multidisciplinary focal prostate therapy team consisting of one interventional radiologist and two urologists. Patients were seen in interventional radiology and urology clinics. During each procedure the number of needle insertions and adjustments was tracked to better evaluate accuracy in clinical practice. Results:The targeting grid and software allowed rapid, repeatable needle insertions with a mean error of 1.05 mm and a standard deviation 0.38 mm. Across 24 prostate-focused procedures (9 biopsies, 14 cryoablations, 1 fluid aspiration), the tools guided interventionalists on their initial insertion of biopsy needles or cryoprobes. In an average procedure, 81.8% of the inserted needles required no adjustment from their first insertion. All procedures achieved technical success during the intervention, satisfying the leading clinician's standards for biopsy sample collection and/or ablation coverage. Conclusions:Phantom and patient trials found that the proposed tools and techniques enabled clinicians to quickly and accurately place their needles in simulated tissue and clinical procedures. This minimal-investment adaptation of a diagnostic scanner for interventional purposes lowers barriers to entry for image-guided prostate interventions, while the trajectory guide's simplicity requires no specialized on-site engineering support and can be readily fabricated, promoting greater ease-of-use.

Abstract Workflows for MRI-guided minimally-invasive neurosurgeries are often time-consuming and complex. Many minimally-invasive interventions utilize magnetic resonance imaging (MRI) to noninvasively visualize internal anatomy and pathologies. This, in conjunction with external trajectory guides, can be used to internally position devices to perform complex surgeries with minimal disruption to the patients’ healthy anatomy. These trajectory guides are typically rigidly attached to the skull and feature adjustable channels through which drills, needles, and /or catheters may be introduced. Trajectories are oriented by iterating between imaging and manipulation of device settings. MRI scans, while offering a great deal of valuable anatomic information, are slow to acquire. Scans of a sufficient resolution for neurosurgery can take on the order of 10 minutes to acquire, depending on field of view. Noniterative approaches could reduce complexity and anesthesia time. This work describes efforts to create and validate a new trajectory guide that enables faster, accurate trajectory guidance in minimally-invasive neurosurgeries. Using new hardware and software, a single scan approach was used to perform drill guidance and device insertion on phantoms and cadaver heads. The proposed methodology accurately guided needles to targets within phantoms and human cadaver brains using a single targeting scan. The initial design produced a radial error of 1.4±0.8mm in phantoms and 1.5±0.8mm in cadaver brains. The proposed device and software accelerate trajectory guidance in minimally-invasive neurosurgeries by reducing the number of acquired scans and procedural steps. This in turn minimizes time under anesthesia.

Introduction: Minimally-invasive surgical techniques for intracerebral hemorrhage (ICH) evacuation use imaging to guide the suction, lysing and/or drainage from the hemorrhage site via various designs. A previous international surgical study has shown that reduction of hematoma volume below 15 ml is indicative of improved long term patient outcomes. The study noted a need for tools to periodically visualize remaining clot during intervention to increase the likelihood of evacuating sufficient clot volumes without endangering rebleeds. Robust segmentation of MRI could guide surgeons and radiologists regarding remaining regions and approaches for prudent evacuation. We thus propose a Convolutional Neural Network (CNN) to identify and autonomously segment clot and peripheral edema in MR images of the brain and generate an estimate of the remaining clot volume. Materials and methods: We used a retrospective, locally-acquired dataset of ICH patient scans taken on 3 T MRI scanners. Three sets of ground truth manual segmentations were independently generated by two imaging scientists and one radiology fellow. Evaluation of clot age was determined based on relative contrast of hemorrhage components and reviewed by a neurosurgeon. Model accuracy was determined by pixel-wise Dice coefficient (DC) calculations between each ground truth manual segmentation and the machine-derived autonomous segmentations.Results: The model produced autonomous segmentations of clot core with an average DC of 0.75 & PLUSMN; 0.21 relative to manual segmentations of the same scans. For edema, it produced segmentations with an average DC of 0.68 & PLUSMN; 0.16 relative to manual. From these pixel-wise segmentations, clot volume can be calculated. Model-produced segmentations underestimated clot volumes by an average of 17% relative to ground-truth.Conclusion: The machine learning models were able to identify and segment volumes of ICH components swiftly and accurately.

For many analysts, the question of whether minimum wage legislation leads to unemployment for unskilled workers is primarily an empirical one. Nearly all economists base their judgment on this matter on the weight of evidence. However, this paper posits a different perspective: that the law necessarily results in unemployment for unskilled workers, and this conclusion arises from pure logic, not empirical evidence. This stance is not widely embraced within mainstream economic circles, as most adhere to the Logical Positivism school of thought. Within this paradigm, claims are either inherently true (and therefore tautological, bearing no implications for real-world issues like unemployment) or they are empirical assertions, which can reflect reality but aren't intrinsically true. In stark contrast, this paper's analysis is rooted in the synthetic a priori—assertions that are inherently true and yet still shed light on economic reality.

With recent advances in cancer therapeutics, there is a great need for improved imaging methods for characterizing cancer onset and progression in a quantitative and actionable way. Collagen, the most abundant extracellular matrix protein in the tumor microenvironment (and the body in general), plays a multifaceted role, both hindering and promoting cancer invasion and progression. Collagen deposition can defend the tumor with immunosuppressive effects, while aligned collagen fiber structures can enable tumor cell migration, aiding invasion and metastasis. Given the complex role of collagen fiber organization and topology, imaging has been a tool of choice to characterize these changes on multiple spatial scales, from the organ and tumor scale to cellular and subcellular level. Macroscale density already aids in the detection and diagnosis of solid cancers, but progress is being made to integrate finer microscale features into the process. Here we review imaging modalities ranging from optical methods of second harmonic generation (SHG), polarized light microscopy (PLM), and optical coherence tomography (OCT) to the medical imaging approaches of ultrasound and magnetic resonance imaging (MRI). These methods have enabled scientists and clinicians to better understand the impact collagen structure has on the tumor environment, at both the bulk scale (density) and microscale (fibrillar structure) levels. We focus on imaging methods with the potential to both examine the collagen structure in as natural a state as possible and still be clinically amenable, with an emphasis on label-free strategies, exploiting intrinsic optical properties of collagen fibers.

Advances in accelerated magnetic resonance imaging (MRI) continue to push the bounds on achievable spatial and temporal resolution while maintaining a clinically acceptable image quality. Validation tools, including numerical simulations, are needed to characterize the repeatability and reproducibility of such methods for use in quantitative imaging applications. We describe the development of a simulation framework for analyzing and optimizing accelerated MRI acquisition and reconstruction techniques used in dynamic contrast enhanced (DCE) breast imaging. The simulation framework, in the form of a digital reference object (DRO), consists of four modules that control different aspects of the simulation, including the appearance and physiological behavior of the breast tissue as well as the MRI acquisition settings, to produce simulated k-space data for a DCE breast exam. The DRO design and functionality are described along with simulation examples provided to show potential applications of the DRO. The included simulation results demonstrate the ability of the DRO to simulate a variety of effects including the creation of simulated lesions, tissue enhancement modeled by the generalized kinetic model, T1-relaxation, fat signal precession and saturation, acquisition SNR, and changes in temporal resolution.

Purpose In current intraoperative MRI (IMRI) methods, an iterative approach is used to aim trajectory guides at intracerebral targets: image MR‐visible features, determine current aim by fitting model to image, manipulate device, repeat. Infrequent updates are produced by such methods, compared to rapid optically tracked stereotaxy used in the operating room. Our goal was to develop a real‐time interactive IMRI method for aiming. Methods The current trajectory was computed from two points along the guide's central axis, rather than by imaging the entire device. These points were determined by correlating one‐dimensional spokes from a radial sequence with the known cross‐sectional projection of the guide. The real‐time platform RTHawk was utilized to control MR sequences and data acquisition. On‐screen updates were viewed by the operator while simultaneously manipulating the guide to align it with the planned trajectory. Accuracy was quantitated in a phantom, and in vivo validation was demonstrated in nonhuman primates undergoing preclinical gene () and cell () delivery surgeries. Results Updates were produced at 5 Hz In 10 phantom experiments at a depth of 48 mm, the cannula tip was placed with radial error of (min, mean, max) = (0.16, 0.29, 0.68) mm. Successful in vivo delivery of payloads to all 14 targets was demonstrated across nine surgeries with depths of (min, mean, max) = (33.3, 37.9, 42.5) mm. Conclusion A real‐time interactive update rate was achieved, reducing operator fatigue without compromising accuracy. Qualitative interpretation of images during aiming was rendered unnecessary by objectively computing device alignment.

Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson's disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD1. Unfortunately, the outcomes are mixed, primarily due to the undefined and unstandardized donor tissues1,2. Generation of induced pluripotent stem cells enables standardized and autologous transplantation therapy for PD. However, its efficacy, especially in primates, remains unclear. Here we show that over a 2-year period without immunosuppression, PD monkeys receiving autologous, but not allogenic, transplantation exhibited recovery from motor and depressive signs. These behavioral improvements were accompanied by robust grafts with extensive DA neuron axon growth as well as strong DA activity in positron emission tomography (PET). Mathematical modeling reveals correlations between the number of surviving DA neurons with PET signal intensity and behavior recovery regardless autologous or allogeneic transplant, suggesting a predictive power of PET and motor behaviors for surviving DA neuron number.

Purpose The aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [ 18 F]FEPPA has the sensitivity for detecting changes in microglial activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (iPSC-mDA). Methods In vivo positron emission tomography (PET) imaging with [ 18 F]FEPPA was used in conjunction with postmortem CD68 immunostaining to evaluate neuroinflammation in the brains of hemiparkinsonian rhesus macaques (n = 6) that received allogeneic iPSC-mDA grafts in the putamen ipsilateral to MPTP administration. Results Based on visual inspection of the imaging data and assessment of radiotracer uptake, nonhuman primates with allogeneic grafts showed increased [ 18 F]FEPPA binding at the graft sites relative to the contralateral putamen. From PET asymmetry analysis of the images, the mean asymmetry index of the monkeys was AI = -0.110 ± 0.025. Evaluation and scoring of CD68 immunoreactivity by an investigator blind to the treatment identified significantly more neuroinflammation in the grafted areas of the putamen compared to the contralateral nucleus (p = 0.0004). [ 18 F]FEPPA PET standard uptake values normalized to the contralateral putamen (SUV norm ) showed a positive correlation with CD68 immunoreactivity ratings in the monkeys (Pearson’s r = 0.83; p = 0.0008). Conclusion These findings reveal that [ 18 F]FEPPA PET is an effective marker for detecting increased microglial activation and demonstrate sufficient sensitivity to detect small changes in neuroinflammation in vivo following allogeneic cell engraftment.

NOTE: The first page of text has been automatically extracted and included below in lieu of an abstract Development of Professional Communication Skills Throughout the BME Curriculum Abstract A sequence of six design courses are required in the undergraduate biomedical engineering curriculum at the University of Wisconsin-Madison. This sequence of courses provide a platform for students to develop and improve their oral and written communication skills. After taking a freshman engineering design course, each student admitted to biomedical engineering in the sophomore year does a team design project each semester for six sequential semesters. The teams work on progressively more challenging real-world projects submitted by clients from around the university and from industry. While advancing their technical and problem-solving skills through successive projects, the students also learn interpersonal and public communication skills through this experience. Introduction Beginning in 1998, we started teaching a sequence of design courses to all students in biomedical engineering beginning when they are admitted to the B.S. degree program in the first semester of their sophomore year1,2,3. Design courses throughout the curriculum form a unique feature of the BME undergraduate degree program. Every BME student registers for a design course and works on a client-based design project every semester for six consecutive semesters. These six design courses constitute a total of eight degree credits. All the courses are one credit except the 3-credit capstone design course in the first semester of the senior year. These design courses are supervised by faculty advisers. Each faculty member has a weekly two-hour meeting in a computer lab with his/her teams. The courses provide a platform for professional communication throughout the curriculum as well as a relevant structure to discuss many issues related to design including intellectual property, professionalism, entrepreneurialism, engineering ethics, and the need for lifelong learning. All the design projects are client-based, real-world design problems, solicited primarily from the medical and life sciences faculty around the university, as well as from biomedical engineering companies. Also we do projects with individuals who have specific rehabilitation needs. The design faculty team reviews the proposed projects and chooses those that are well matched to the students’ abilities and likely to result in physical prototypes. Once a team of four students is formed and chooses a project, the team interacts with their client and advisor to define the specifications for their project and maintains a dialog with their client throughout the course. The client provides meaningful feedback as the design progresses as well as access to the appropriate clinical or research setting. Faculty are fully responsible for all aspects of the design courses. We do not use teaching assistants. The Figure shows relationships among the six design courses. As part of the overall goals of learning the design process and creating a physical prototype, each of the courses has different individual goals.

Purpose The aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [ 18 F]FEPPA has the sensitivity for detecting changes in CD68-positive microglial/macrophage activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (iPSC-mDA). Methods In vivo positron emission tomography (PET) imaging with [ 18 F]FEPPA was used in conjunction with postmortem CD68 immunostaining to evaluate neuroinflammation in the brains of hemiparkinsonian rhesus macaques ( n = 6) that received allogeneic iPSC-mDA grafts in the putamen ipsilateral to MPTP administration. Results Based on assessment of radiotracer uptake and confirmed by visual inspection of the imaging data, nonhuman primates with allogeneic grafts showed increased [ 18 F]FEPPA binding at the graft sites relative to the contralateral putamen. From PET asymmetry analysis of the images, the mean asymmetry index of the monkeys was AI = − 0.085 ± 0.018. Evaluation and scoring of CD68 immunoreactivity by an investigator blind to the treatment identified significantly more neuroinflammation in the grafted areas of the putamen compared to the contralateral putamen ( p = 0.0004). [ 18 F]FEPPA PET AI showed a positive correlation with CD68 immunoreactivity AI ratings in the monkeys (Spearman’s ρ = 0.94; p = 0.005). Conclusion These findings reveal that [ 18 F]FEPPA PET is an effective marker for detecting increased CD68-positive microglial/macrophage activation and demonstrates sufficient sensitivity to detect changes in neuroinflammation in vivo following allogeneic cell engraftment.

BACKGROUND:An early-life anxious temperament (AT) is a risk factor for the development of anxiety, depression, and comorbid substance abuse. We validated a nonhuman primate model of early-life AT and identified the dorsal amygdala as a core component of AT's neural circuit. Here, we combine RNA sequencing, viral-vector gene manipulation, functional brain imaging, and behavioral phenotyping to uncover AT's molecular substrates. METHODS:In response to potential threat, AT and brain metabolism were assessed in 46 young rhesus monkeys. We identified AT-related transcripts using RNA-sequencing data from dorsal amygdala tissue (including central nucleus of the amygdala [Ce] and dorsal regions of the basal nucleus). Based on the results, we overexpressed the neurotrophin-3 gene, NTF3, in the dorsal amygdala using intraoperative magnetic resonance imaging-guided surgery (n = 5 per group). RESULTS:This discovery-based approach identified AT-related alterations in the expression of well-established and novel genes, including an inverse association between NTRK3 expression and AT. NTRK3 is an interesting target because it is a relatively unexplored neurotrophic factor that modulates intracellular neuroplasticity pathways. Overexpression of the transcript for NTRK3's endogenous ligand, NTF3, in the dorsal amygdala resulted in reduced AT and altered function in AT's neural circuit. CONCLUSIONS:Together, these data implicate neurotrophin-3/NTRK3 signaling in the dorsal amygdala in mediating primate anxiety. More generally, this approach provides an important step toward understanding the molecular underpinnings of early-life AT and will be useful in guiding the development of treatments to prevent the development of stress-related psychopathology.

Dopamine (DA) levels in the striatum are increased by many therapeutic drugs, such as methylphenidate (MPH), which also alters behavioral and cognitive functions thought to be controlled by the PFC dose-dependently. We linked DA changes and functional connectivity (FC) using simultaneous [18F]fallypride PET and resting-state fMRI in awake male rhesus monkeys after oral administration of various doses of MPH. We found a negative correlation between [18F]fallypride nondisplaceable binding potential (BPND) and MPH dose in the head of the caudate (hCd), demonstrating increased extracellular DA resulting from MPH administration. The decreased BPND was negatively correlated with FC between the hCd and the PFC. Subsequent voxelwise analyses revealed negative correlations with FC between the hCd and the dorsolateral PFC, hippocampus, and precuneus. These results, showing that MPH-induced changes in DA levels in the hCd predict resting-state FC, shed light on a mechanism by which changes in striatal DA could influence function in the PFC.SIGNIFICANCE STATEMENT Dopamine transmission is thought to play an essential role in shaping large scale-neural networks that underlie cognitive functions. It is the target of therapeutic drugs, such as methylphenidate (Ritalin), which blocks the dopamine transporter, thereby increasing extracellular dopamine levels. Methylphenidate is used extensively to treat attention deficit hyperactivity disorder, even though its effects on cognitive functions and their underlying neural mechanisms are not well understood. To date, little is known about the link between changes in dopamine levels and changes in functional brain organization. Using simultaneous PET/MR imaging, we show that methylphenidate-induced changes in endogenous dopamine levels in the head of the caudate predict changes in resting-state functional connectivity between this structure and the prefrontal cortex, precuneus, and hippocampus.

Abstract INTRODUCTION The spatial and temporal resolution limits of functional MRI (fMRI) brain mapping provide primarily correlative information on brain connectivity. Determining how one region causally modulates and mediates activity in other regions remains difficult with fMRI. We demonstrate a simple means to add causality in resting state functional connectivity MRI (rs-fcMRI) using techniques developed first for convection-enhanced delivery (CED) of therapeutics. Here we use CED to guide and monitor pharmacologic alteration of a local brain region in anaesthetized Rhesus monkeys while monitoring rs-fcMRI signal changes. METHODS Pre-surgical MRI was used to determine skull locations for craniotomies for installation of NavigusTMbrain ports in two untrained monkeys slated for euthanasia. The ports were aligned in real–time to provide trajectories aimed at the central nucleus of the amygdala (CeA). Fused silica catheters were then inserted into the CeA where 24 mg of muscimol (inhibitory agent) was infused in 24 ml of buffered solution under pressure over 12 minutes, first on the right side and then on the left side. rs-fcMRI studies were done for 45 minutes before and after the unilateral infusion and then after the bilateral infusion. RESULTS Catheters were successfully aligned and inserted into the CeA targets with sub-mm accuracy. T2-weighted imaging detected the enhanced T2 from the infusion’s buffer. Pre-infusion rs-fcMRI provides results consistent with prior studies, which have shown that the CeA is most strongly connected to the contralateral CeA. This connectivity was significantly reduced following both unilateral and bilateral injections of muscimol into the CeA, demonstrating the effectiveness of the muscimol infusions. Conditional Grainger Causality (CGC) analysis shows unexpected new connectivity after the unilateral infusion. Upon the bilateral infusion, global effective connectivity in the region is reduced. CONCLUSION Expected and unexpected changes in resting state functional connectivity resulted from unilateral and bilateral infusions of inhibitory agents.

New dynamic MRI methods hold promise in better characterization of the complex structure and heterogeneous treatment response of brain tumors. These methods utilize assumptions to reduce the data samples needed to produce high temporal and spatial resolution images with complex, iterative reconstructions. Determining how these methods depict actual brain tumor pathology is difficult due to lack of a gold standard. We therefore tailor an existing digital tool, built originally to simulate dynamic MRI breast studies, to assess the performance of new dynamic methods if applied to brain cancer. The tool permits a tumor of customizable shape featuring an inner core and an adjustable surrounding rim to be overlaid on a digital 3-D brain model, which we acquired from an online database called BrainWeb, with segmented brain tissue layers. We used existing capabilities in the tool to assign pharmacokinetic parameters to each tumor region to simulate necrotic cores and rims of varying width that represent spatially varying levels of enhancement due to tumor pathology and/or radiation necrosis. The tool then computes the corresponding MR k-space data for any proposed MR sampling trajectory during a simulated passage of a contrast agent. The simulated MR k-space data can then be input to any proposed reconstruction to produce a simulated time course of image volumes. Performance of proposed dynamic MR imaging methods can be measured against the digital truth prior to clinical trials through methods including: the structural similarity (SSIM) index over the lesion region-of-interest, comparing calculated vs. assigned pharmacokinetic parameters, and root-mean-square error. We are using this tool to estimate the performance, in brain applications, of a 3-D radial acquisition and reconstruction method with compressed sensing and local low rank that was previously demonstrated to produce 0.8 mm resolution in a 10 second frame rate in bilateral breast screening.

Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. All dogs were treated with tibial plateau leveling osteotomy (TPLO) on the unstable stifle and a single intra-articular application of PRP-collagen in the stable partial CR stifle. Dogs were evaluated at the time of diagnosis, and at 10-weeks and 12-months after treatment. We evaluated correlation between both development of complete CR and time to complete CR with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla magnetic resonance (MR) imaging, and bilateral stifle arthroscopy. Additionally, histologic evaluation of synovial biopsies, C-reactive protein (CRP) concentrations in serum and synovial fluid, and synovial total nucleated cell count, were determined. Results indicated that a single application of PRP-collagen in partial CR stifles of client owned dogs is not an effective disease-modifying therapy for the prevention of progression to complete CR. Radiographic effusion, arthroscopic evaluation of cranial cruciate ligament (CrCL) damage, and MR assessment of ligament fiber tearing in partial CR stifles correlated with progression to complete CR over the 12-month follow-up period. We determined that the best predictive model for development of complete CR in PRP-collagen treated partial CR stifles included variables from multiple diagnostic modalities.