Association of vastus lateralis diffusion properties with in vivo quadriceps contractile function in premenopausal women.

BACKGROUND: Diffusion tensor imaging (DTI) parameters correlate with muscle fiber composition, but it is unclear how these relate to in vivo contractile function. PURPOSE: To determine the relationship between DTI parameters of the vastus lateralis (VL) and in vivo knee extensor contractile. METHODS: Thirteen healthy, premenopausal women underwent magnetic resonance imaging of the mid-thigh to determine patellar tendon moment arm length and quadriceps cross-sectional area. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the VL were determined using diffusion tensor imaging (DTI). Participants underwent an interpolated twitch (ITT) experiment before and after a fatiguing concentric-eccentric isokinetic knee extension (60°·s-1 ). During the ITT, supramaximal electrical stimuli were delivered to elicit twitch responses from the knee extensors before, during, and after a maximal voluntary isometric contraction (MVIC). Knee extensor-specific tension during twitch and MVIC were calculated from isometric torque data. Pearson's correlations were used to determine the relationship between muscle contractile properties and DTI parameters. RESULTS: MD and RD were moderately correlated with peak twitch force and rate of force development. FA and AD were moderately inversely related to percent change in MVIC following exercise. CONCLUSION: MD and RD are associated with in vivo quadriceps twitch properties but not voluntary strength, which may reflect the mechanical properties of constituent fiber types. FA and AD appear to relate to MVIC strength following fatiguing exercise.

T1ρ imaging as a non-invasive assessment of collagen remodelling and organization in human skeletal muscle after ligamentous injury.

Dysregulation and fibrosis of the extracellular matrix (ECM) in skeletal muscle is a consequence of injury. Current ECM assessment necessitates muscle biopsies to evaluate alterations to the muscle ECM, which is often not practical in humans. The goal of this study was to evaluate the potential of a magnetic resonance imaging sequence that quantifies T1ρ relaxation time to predict ECM collagen composition and organization. T1ρ imaging was performed and muscle biopsies obtained from the involved and non-involved vastus lateralis muscle on 27 subjects who had an anterior cruciate ligament (ACL) tear. T1ρ times were quantified via monoexponential decay curve fitted to a series of T1ρ-weighted images. Several ECM indices, including collagen content and organization, were obtained using immunohistochemistry and histochemistry in addition to hydroxyproline. Model selection with multiple linear regression was used to evaluate the relationships between T1ρ times and ECM composition. Additionally, the ACL-deficient and healthy limb were compared to determine sensitivity of T1ρ to detect early adaptations in the muscle ECM following injury. We show that T1ρ relaxation time was strongly associated with collagen unfolding (t = 4.093, P = 0.0007) in the ACL-deficient limb, and collagen 1 abundance in the healthy limb (t = 2.75, P = 0.014). In addition, we show that T1ρ relaxation time is significantly longer in the injured limb, coinciding with significant differences in several indices of collagen content and remodelling in the ACL-deficient limb. These results support the use of T1ρ to evaluate ECM composition in skeletal muscle in a non-invasive manner. KEY POINTS: Dysregulation and fibrotic transformation of the skeletal muscle extracellular matrix (ECM) is a common pathology associated with injury and ageing. Studies of the muscle ECM in humans have necessitated the use of biopsies, which are impractical in many settings. Non-invasive MRI T1ρ relaxation time was validated to predict ECM collagen composition and organization with aligned T1ρ imaging and biopsies of the vastus lateralis in the healthy limb and anterior cruciate ligament (ACL)-deficient limb of 27 subjects. T1ρ relaxation time was strongly associated with collagen abundance and unfolding in the ACL-deficient limb, and T1ρ relaxation time was strongly associated with total collagen abundance in the healthy limb. T1ρ relaxation time was significantly longer in the ACL-deficient limb, coinciding with significant increases in several indices of muscle collagen content and remodelling supporting the use of T1ρ to non-invasively evaluate ECM composition and pathology in skeletal muscle.

Comparison of twice refocused spin echo versus stimulated echo diffusion tensor imaging for tracking muscle fibers.

PURPOSE: To compare the precision of measuring the pennation angle and fiber length in the vastus lateralis (VL) using two distinctly different diffusion tensor imaging (DTI) sequences. MATERIALS AND METHODS: We imaged the thigh of 10 normal subjects on a 3T magnetic resonance (MR) imager with twice refocused spin echo (TRSE) and stimulated echo (STEAM) DTI-MRI techniques. Both techniques took the same total acquisition time and employed the same diffusion weighting and gradient directions. Using the diffusion tensor images produced by each sequence, muscle fiber bundles were tracked from the aponeurosis by following the first eigenvector of the diffusion tensor. From these tracks we calculated the pennation angle and fiber length. RESULTS: The STEAM acquisition resulted in significantly higher signal-to-noise ratio (SNR), lower apparent diffusion coefficient (ADC), higher fractional anisotropy (FA) values, and longer fibers than TRSE. Although no difference in the pennation angle between the two acquisitions was found, the TRSE sequence had a significantly greater within-subject dispersion in the pennation angle of tracked fibers, which may indicate a reduction in the coherence of fiber bundles. CONCLUSION: DTI of muscle using a STEAM acquisition resulted in significant improvements in the SNR and FA, resulting in tracking a larger number of muscle fiber bundles over longer distances and with less within-subject dispersion.

Three-dimensional simulation of mass transfer in artificial kidneys.

In this work, the three-dimensional velocity and concentration fields on both the blood and dialysate sides in an artificial kidney were simulated, taking into account the effects of the flow profiles induced by the inlet and outlet geometrical structures and the interaction between the flows of blood and dialysate. First, magnetic resonance imaging experiments were performed to validate the mathematical model. Second, the effects of the flow profiles induced by the blood and dialysate inlet and outlet geometrical structures on mass transfer were theoretically investigated. Third, the clearance of toxins was compared with the clearance value calculated by a simple model that is based on the ideal flow profiles on both the blood and dialysate sides. Our results show that as the blood flow rate increases, the flow field on the blood side becomes less uniform; however, as the dialysate flow rate increases, the flow field on the dialysate side becomes more uniform. The effect of the inlet and outlet geometrical structures of the dialysate side on the velocity and concentration fields is more significant than that of the blood side. Due to the effects of the flow profiles induced by the inlet and outlet geometrical structures, the true clearance of toxins is lower than the ideal clearance, especially when the dialysate flow rate is low or the blood flow rate is high. The results from this work are significant for the structural optimization of artificial kidneys and the accurate prediction of toxin clearance.

The Efficacy of Blood Flow Restriction Training to Improve Quadriceps Muscle Function after ACL Reconstruction.

BACKGROUND: Blood flow restriction training (BFRT) is a popular rehabilitation intervention after anterior cruciate ligament reconstruction (ACLR). However, there are a lack of clinical trials establishing the efficacy of using BFRT during rehabilitation to improve quadriceps muscle function. PURPOSE: To evaluate the efficacy of blood flow restriction training to improve quadriceps muscle strength, morphology, and physiology, and knee biomechanics in individuals after ACLR in a double-blind, randomized, placebo-controlled clinical trial (NCT03364647). METHODS: 48 athletes (20 females/28 males) were randomly assigned to low-load strength training with active BFRT or standard of care strength training with a sham unit. Treatment occurred for 1-month pre-surgery and 4-5 months post-surgery with both groups following the same standard rehabilitation protocol. Outcome variables were measured at baseline and 4-5 months post-surgery. Quadriceps muscle strength (isometric and isokinetic peak torque and rate of torque development) was measured on an isokinetic dynamometer. Quadriceps muscle morphology (physiological cross-sectional area, fibrosis) was determined using magnetic resonance imaging. Quadriceps muscle physiology (fiber type, fiber cross-sectional area, satellite cell abundance, collagen content, fibro-/adipo-genic progenitor cells) was evaluated with muscle biopsies of the vastus lateralis. Knee extensor moment and knee flexion angle were measured via three-dimensional gait analysis. Change scores were calculated as: post-intervention-baseline. Two sample t-tests were then used to assess between-group differences for each outcome variable. RESULTS: No significant between-group differences were found for any outcome variable. CONCLUSIONS: The addition of BFRT to a rehabilitation program for athletes pre- and post- ACLR was no more effective than standard rehabilitation for improving quadriceps muscle function. Clinicians should consider the value of BFRT relative to the cost, time, and discomfort for patients in light of these results.

Block copolymer cross-linked nanoassemblies improve particle stability and biocompatibility of superparamagnetic iron oxide nanoparticles.

PURPOSE: To develop cross-linked nanoassemblies (CNAs) as carriers for superparamagnetic iron oxide nanoparticles (IONPs). METHODS: Ferric and ferrous ions were co-precipitated inside core-shell type nanoparticles prepared by cross-linking poly(ethylene glycol)-poly(aspartate) block copolymers to prepare CNAs entrapping Fe(3)O(4) IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe(3)O(4) IONPs (Citrate-IONPs). RESULTS: CNA-IONPs, approximately 30 nm in diameter, showed no precipitation in water, PBS, or a cell culture medium after 3 or 30 h, at 22, 37, and 43°C, and 1, 2.5, and 5 mg/mL, whereas Citrate-IONPs agglomerated rapidly (> 400 nm) in all aqueous media tested. No cytotoxicity was observed in a mouse brain endothelial-derived cell line (bEnd.3) exposed to CNA-IONPs up to 10 mg/mL for 30 h. Citrate-IONPs (> 0.05 mg/mL) reduced cell viability after 3 h. CNA-IONPs retained the superparamagnetic properties of entrapped IONPs, enhancing T2-weighted magnetic resonance images (MRI) at 0.02 mg/mL, and generating heat at a mild hyperthermic level (40 ~ 42°C) with an alternating magnetic field (AMF). CONCLUSION: Compared to citric acid coating, CNAs with a cross-linked anionic core improved particle stability and biocompatibility of IONPs, which would be beneficial for future MRI and AMF-induced remote hyperthermia applications.

Development of bespoke hardware and software to enable testing of a novel method of managing the charge and discharge of series-connected battery packs.

The novel feature of the method of battery management under development and testing is that routine balancing of the cells is eliminated throughout the service life of the battery pack. This requires preparation of the battery cells and configuration of the rigs in such a way as to ensure that the cells are accurately balanced on assembly and that thereafter there is no cell-to-cell variation in charge current or load at any time, measured to a low microamp level. In addition, the method requires a special charge control algorithm which was devised in order to accommodate cell-to-cell variations in capacity and dynamic response. Comprehensive experimental testing of this method, which is fully described in the associated paper (Hardy et al., 2023), required the development of hardware and software which would combine the necessary functions of a battery test rig and a battery management system capable of carrying out the special method of charge control described below. These included:•The automated control of contactors, loads and chargers to perform multiple charge/discharge cycles to predetermined patterns of current and maximum and minimum cell voltages.•Monitoring of cell voltages, current and temperature and the provision of test and diagnostic data.•Performing the safety functions of a Battery Management System to ensure that no cell was permitted to exceed limitations of current, voltage or temperature. The hardware and software were developed through three phases of testing with the operational principles (but not all the hardware and software elements) carrying over from one phase to the next.

Quantitative assessments of image intensifier distortion induced by weak (Sub-Gauss) magnetic fields during fluoroscopically-guided procedures.

BACKGROUND: Fluoroscopically-guided procedures at our hospital have been aborted due to sigmoidal distortion (S-distortion) when an image intensifier (II) system is used in a surgical environment distant from any apparent sources of strong magnetic fields, such as a nearby magnetic resonance imaging (MRI) scanner. Clearly, current clinical practice fails to account for the impact of ambient weak magnetic fields and/or other contributing factors on S-distortion induction. PURPOSE: This study attempts to quantitatively assess the threshold level of magnetic field, along with other potential factors, that can induce intolerable S-distortion during image-intensified fluoroscopically-guided procedures. We will also discover the origins of such level of magnetic field in typical surgical facilities and provide our practical mitigation strategies accordingly. METHODS: Ten surgical facilities and their accessory equipment (e.g., surgical tables) were screened using an AC/DC gaussmeter for the distribution and magnitude of magnetic field (magnetic flux density). A 'hot spot' of magnetic field was identified to further investigate the induction of S-distortion by scanning a titanium rod phantom using a GE OEC 9900 Elite II system placed at increasing distance from the 'hot spot' corresponding to decreasing magnetic field experienced by the II. The measurements were compared to that on a 'cold spot', and a GE flat panel detector (FPD) fluoroscopy was used as the negative control. Rod phantoms made of various magnetic susceptible materials (titanium, steel, aluminium, and copper) were scanned to explore the potential effects of implant material on S-distortion. An upper extremity anthropomorphic phantom was imaged on various surgical tables to mimic clinical sceneries. The GE II model and Siemens ARCADIS Orbic II model were compared to evaluate if S-distortion induction varied among different II models. Two metrics, angle of rotation (θ) and deviation/length ratio, were used to quantify the degree of S-distortion. Three designs of external magnetic shielding were evaluated for mitigating S-distortion. RESULTS: We identified static magnetic fields up to 2500 µT and 70 µT on the floor and at 1-meter height, respectively, in random locations of surgical facilities. A large variation of magnetic field (64 ± 20 µT) was detected on the surface of surgical tables, with background magnetic fields of ∼35 µT. Quantitative assessments demonstrated that even weak magnetic fields at sub-Gauss level (<100 µT) could induce noticeable distortion artifacts, deemed unacceptable (θ > 4°). S-distortion was independent of the implant material being imaged but dependent on the II model - the threshold magnetic fields (4° distortion induction) were as low as 47 µT and 94 µT for the GE and Siemens II models. Mitigation possibilities of S-distortion include relocating the II to an area with subthreshold magnetic fields and shielding the II utilizing cylindrical mu-metal shields with an extension for alleviating the effect of openings. CONCLUSIONS: This work demonstrates that ambient sub-Gauss magnetic fields originating from any possible sources in a surgical environment have to be carefully considered when performing an image-intensified fluoroscopically-guided procedure, because such weak magnetic fields are likely able to induce unacceptable S-distortion artifacts in the acquired X-ray images leading to undesirable surgical outcomes.

Multilevel Approach to Support Diversity, Equity and Inclusion in Radiology.

Integrating diversity into healthcare systems has its challenges and advantages. Academic medicine strives to expand the diversity of the healthcare workforce. The Association of University Radiologists (AUR) put together a task force to review the concept of Diversity, Equity and Inclusion (DEI) as it pertains to Radiology and to propose strategies for better integrating DEI in Radiology. We present several measures aimed at the trainee, leadership, management and professional society levels to empower DEI in Radiology.

Blood flow Restriction training After patellar INStability (BRAINS Trial).

BACKGROUND: Patellar instability is a common and understudied condition that disproportionally affects athletes and military personnel. The rate of post-traumatic osteoarthritis that develops following a patellar dislocation can be up to 50% of individuals 5-15 years after injury. Conservative treatment is the standard of care for patellar instability however, there are no evidence-informed rehabilitation guidelines in the scientific literature. The purpose of this study is to assess the effectiveness of blood-flow restriction training (BFRT) for patellar instability. Our hypotheses are that this strategy will improve patient-reported outcomes and accelerate restoration of symmetric strength and knee biomechanics necessary to safely return to activity. METHODS/DESIGN: This is a parallel-group, superiority, randomized, double-blinded, placebo-controlled clinical trial at the University of Kentucky, sports medicine clinic that aims to recruit 78 patients with acute patellar dislocations randomly allocated into two groups: (1) sham BFRT and (2) BFRT. Both groups will receive the current standard of care physical therapy 3 times per week for up to 9 weeks. Physical therapy sessions will consist of typical standard of care treatment followed by BFRT or sham BFRT. Primary outcomes include the Norwich Patellar Instability Scale, quadriceps strength, and imaging and biochemical biomarkers of cartilage degradation. DISCUSSION: The current standard of care for non-operative treatment of patellar instability is highly variable does not adequately address the mechanisms necessary to restore lower extremity function and protect the long-term health of articular cartilage following injury. This proposed novel intervention strategy uses an easily implementable therapy to evaluate if BFRT significantly improves patient-reported outcomes, function, and joint health over the first year of recovery. TRIAL REGISTRATION: Blood Flow Restriction Training, Aspiration, and Intraarticular Normal Saline (BRAINS) NCT04554212 . Registered on 18 September 2020.

The paradox of productivity during quarantine: an agent-based simulation.

ABSTRACT: Economies across the globe were brought to their knees due to lockdowns and social restriction measures to contain the spread of the SARS-CoV-2, despite the quick switch to remote working. This downfall may be partially explained by the "water cooler effect", which holds that higher levels of social interaction lead to higher productivity due to a boost in people's mood. Somewhat paradoxically, however, there are reports of increased productivity in the remote working scenario. Here we address quantitatively this issue using a variety of experimental findings of social psychology that address the interplay between mood, social interaction and productivity to set forth an agent-based model for a workplace composed of extrovert and introvert agent stereotypes that differ solely on their propensities to initiate a social interaction. We find that the effects of curtailing social interactions depend on the proportion of the stereotypes in the working group: while the social restriction measures always have a negative impact on the productivity of groups composed predominantly of introverts, they may actually improve the productivity of groups composed predominantly of extroverts. Our results offer a proof of concept that the paradox of productivity during quarantine can be explained by taking into account the distinct effects of the social distancing measures on extroverts and introverts.

Surgical methodology and protocols for preventing implanted cerebral catheters from becoming obstructed during and after neurosurgery.

BACKGROUND: Convection Enhanced Delivery (CED) into targeted brain areas has been tested in animal models and clinical trials for the treatment of various neurological diseases. NEW METHOD: We used a series of techniques, to in effect, maintain positive pressure inside the catheter relative to the outside, that included a hollow stylet, a high volume bolus of solution to clear the line, a low and slow continuous flow rate during implantation, and heat sealing the catheter at the time of implantation. RESULTS: 120 catheters implanted into brain parenchyma of 89 adult female rhesus monkeys across four sets of experiments. After experiencing a high delivery failure rate - non patent catheters - (19 %) because of tissue entrapment and debris and/or blood clots in the catheter tip, we developed modifications, including increasing the bolus infusion volume from 10 to 20 µl such that by the third experiment, the failure rate was 8 % (1 of 12 implants). Increasing the bolus volume to 100 µl and maintaining positive pressure in the catheter during preparation and implantation yielded a failure rate of 0 % (0/12 implants) by the fourth experiment. COMPARISON WITH EXISTING METHODS: We provide a retrospective analysis to reveal how several different manipulations affect catheter patency and how post-op MRI examination is essential for assessing catheter patency in situ. CONCLUSIONS: The results of the present study identified that the main cause of the catheter blockages were clots that rendered the catheter non-patent. We resolved this by modifying the surgical procedures that prevented these clots from forming.

Calculating T2 in images from a phased array receiver.

Images reconstructed from multielement, phased array coils and presented as the square root of the sum of the squares of the signals received by the individual elements have a distribution of signal and noise that distorts the relationship between the image intensity and the underlying signal. The distortion is accentuated for long echo times for which the signal-to-noise ratio (SNR) may be low. When measuring T(2) or T(2)* this signal distortion leads to biased estimates of these parameters. We demonstrate this effect and its dependence on the image SNR and the number of elements in a phased array coil. We evaluated the effects of four techniques for calculating T(2) from data acquired in phased array coils (log transform, least squares, lookup table correction, and maximum likelihood [ML] estimation). The ML estimation gave the most accurate T(2) in the presence of this bias.

Development of a Web-based Curriculum to Prepare Diagnostic Radiology Residents during Post-Graduate Year 1 by Promoting Learning via Spaced Repetition and Interim Testing: If You Build It, Will They Come?

RATIONALE AND OBJECTIVES: The purpose of this pilot project was to determine the feasibility of creating a single web-based resource to allow independent study for pre-radiology interns during their first post-graduate year of training, and to measure intern use of and satisfaction with this resource. MATERIALS AND METHODS: A web-based curriculum, based on the principles of spaced learning and interim testing, was created and housed on an institutional learning management system. The curriculum consisted of narrated, interactive learning modules, electronic flashcards, and quizzes. We monitored the use of this curriculum by six pre-radiology interns. Surveys were completed to assess resident satisfaction. RESULTS: 73% of the total learning modules were completed. Of the completed modules, 90% were completed in either the first or the last three months of the study. The total hours spent reviewing the flashcards during the entire study period ranged from <1 to 7 hours. 67% of the quizzes were completed. Survey results showed that the learners perceived the course as a useful resource and reported high satisfaction with the curriculum. CONCLUSION: Creating a web-based curriculum capable of monitoring intern use is feasible. There was variable use of the different components of the curriculum with clear clustering of use at the beginning and end of the study period. The users perceived the course as a useful resource and reported high satisfaction with the curriculum.

Effect of Blood Flow Restriction Training on Quadriceps Muscle Strength, Morphology, Physiology, and Knee Biomechanics Before and After Anterior Cruciate Ligament Reconstruction: Protocol for a Randomized Clinical Trial.

BACKGROUND: Despite best practice, quadriceps strength deficits often persist for years after anterior cruciate ligament reconstruction. Blood flow restriction training (BFRT) is a possible new intervention that applies a pressurized cuff to the proximal thigh that partially occludes blood flow as the patient exercises, which enables patients to train at reduced loads. This training is believed to result in the same benefits as if the patients were training under high loads. OBJECTIVE: The objective is to evaluate the effect of BFRT on quadriceps strength and knee biomechanics and to identify the potential mechanism(s) of action of BFRT at the cellular and morphological levels of the quadriceps. DESIGN: This will be a randomized, double-blind, placebo-controlled clinical trial. SETTING: The study will take place at the University of Kentucky and University of Texas Medical Branch. PARTICIPANTS: Sixty participants between the ages of 15 to 40 years with an ACL tear will be included. INTERVENTION: Participants will be randomly assigned to (1) physical therapy plus active BFRT (BFRT group) or (2) physical therapy plus placebo BFRT (standard of care group). Presurgical BFRT will involve sessions 3 times per week for 4 weeks, and postsurgical BFRT will involve sessions 3 times per week for 4 to 5 months. MEASUREMENTS: The primary outcome measure was quadriceps strength (peak quadriceps torque, rate of torque development). Secondary outcome measures included knee biomechanics (knee extensor moment, knee flexion excursion, knee flexion angle), quadriceps muscle morphology (physiological cross-sectional area, fibrosis), and quadriceps muscle physiology (muscle fiber type, muscle fiber size, muscle pennation angle, satellite cell proliferation, fibrogenic/adipogenic progenitor cells, extracellular matrix composition). LIMITATIONS: Therapists will not be blinded. CONCLUSIONS: The results of this study may contribute to an improved targeted treatment for the protracted quadriceps strength loss associated with anterior cruciate ligament injury and reconstruction.

Perceptual and Interpretive Error in Diagnostic Radiology-Causes and Potential Solutions.

Interpretation of increasingly complex imaging studies involves multiple intricate tasks requiring visual evaluation, cognitive processing, and decision-making. At each stage of this process, there are opportunities for error due to human factors including perceptual and ergonomic conditions. Investigation into the root causes of interpretive error in radiology first began over a century ago. In more recent work, there has been increasing recognition of the limits of human image perception and other human factors and greater acknowledgement of the role of the radiologist's environment in increasing the risk of error. This article reviews the state of research on perceptual and interpretive error in radiology. This article focuses on avenues for further error examination, and strategies for mitigating these errors are discussed. The relationship between artificial intelligence and interpretive error is also considered.

Nanotemplate-engineered nanoparticles containing gadolinium for magnetic resonance imaging of tumors.

PURPOSE: To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors. METHODS: Nanoparticles containing phospholipid-chelates (phosphoethanolamine diethylenetriaminepentaacetate) and DSPE-PEG (MW5000) were prepared from Brij 78 and stearyl alcohol using the nanotemplate engineering approach. After addition of GdCl3, the presence of gadolinium on the surface of nanoparticles was quantified using inductively coupled plasma atomic emission spectroscopy. The in vitro relaxivities of the Gd-NPs in phosphate buffered saline were assessed at 4.7 T. The conditional binding constants of nanoparticle formulations were determined spectrophotometrically by competitive titration. Transmetallation kinetics of Gd from nanoparticles with Cu2+ and Zn2+ as the competing ions was measured in acetate buffer. The biodistribution profiles, pharmacokinetics, and contrast enhancement in tumor region was studied after administration of Gd-NPs to nude mice bearing A549 lung carcinoma xenografts. RESULTS: Gd-NPs with an average diameter of 138 nm possessing surface chelating functions were prepared from GRAS (generally regarded as safe) materials. The longitudinal relaxivity (r1) and transverse relaxivity (r2) of Gd-NPs in 10% fetal bovine serum at 4.7 T were 7.1 (+/-0.2) and 13.0 (+/-0.7) 1/mM/s, respectively. These pegylated Gd-NPs had enhanced relaxivities and exhibited particle size stability, sufficient binding affinity, and kinetic inertness under physiologic conditions. The contrast enhancement in tumors was demonstrated 40, 120, and 360 minutes after intravenous injection of Gd-NPs at a dose of 0.1 mmol Gd/kg. The Gd plasma concentration of Gd-NPs over a period of 24 hours fit a two-compartmental model with Cl sys = 0.89 mL/h and MRT = 5.93 h. The amount of Gd that accumulated in the tumor region was consistent with the estimated value obtained by T1 measurements using MR imaging. CONCLUSION: Pegylated nanoparticles composed of biocompatible, biodegradable materials and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal and accumulated sufficiently in tumors, demonstrating their utility as potential magnetic resonance imaging tumor contrast enhancement agents.

Pharmacological MRI (phMRI) monitoring of treatment in hemiparkinsonian rhesus monkeys.

There is a great need for the development of noninvasive, highly sensitive, and widely available imaging methods that can potentially be used to longitudinally monitor treatment of Parkinson's disease (PD). Here we report the monitoring of GDNF-induced functional changes of the basal ganglia in hemiparkinsonian monkeys via pharmacological MRI measuring the blood oxygenation level-dependent (BOLD) response to a direct dopamine agonist (apomorphine, APO). After testing BOLD responsiveness to APO in their normal state, two additional scans were taken with the same dose of APO stimulation after induced parkinsonism. Then all animals were chronically treated with GDNF for 18 weeks by a programmable pump and catheter system. The catheter was surgically implanted into the right putamen and connected to the pump via flexible polyurethane tubing, phMRI scans were taken at both 6 and 18 weeks while they received 22.5 microg of GDNF per day. In addition, behavioral changes were monitored throughout the entire study. The primary finding of this study was that APO-evoked activations in the DA denervated putamen were attenuated by the chronic intraputamenal infusion of GDNF accompanied by improvements of parkinsonian features, movement speed, and APO-induced rotation compared to data collected before the chronic GDNF treatment. The results suggest that phMRI methods in combination with administration of a selective DA agonist may be useful for monitoring neurorestorative therapies in PD patients in the future.

Objectively measuring effects of electro-acupuncture in parkinsonian rhesus monkeys.

Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson's disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations. All animals were evaluated for behavior and phMRI responses under normal, parkinsonian, parkinsonian with EA treatment and parkinsonian after EA treatment conditions. Stable parkinsonian features were observed in all animals prior to entering the EA study and positive responses to levodopa (L-dopa) challenge were also seen in all animals. The results demonstrated that chronic EA treatments could significantly improve the movement speed and the fine motor performance time during the period of EA treatments, and the effectiveness of EA could be detected even 3 months after the EA treatment. The phMRI data revealed that chronic EA treatments could alter neuronal activity in the striatum, primary motor cortex (M1), cingulate gyrus and global pallidus externa (GPe) in the ipsilateral hemisphere to MPTP lesions. As seen in the changes of parkinsonian features, the residual effects of phMRI responses to apomorphine (APO) challenge could also be found in the aforementioned areas. The results strongly suggest that anti-parkinsonian effects of EA can be objectively assessed, and the method used in the present study could be translated into the human clinic with some minor modifications.