Distinct local and brain-wide networks are activated by optogenetic stimulation of neurons specific to each layer of motor cortex.

Primary motor cortex (M1) consists of a stack of interconnected but distinct layers (L1-L6) which affect motor control through large-scale networks. However, the brain-wide functional influence of each layer is poorly understood. We sought to expand our knowledge of these layers' circuitry by combining Cre-driver mouse lines, optogenetics, fMRI, and electrophysiology. Neuronal activities initiated in Drd3 neurons (within L2/3) were mainly confined within M1, while stimulation of Scnn1a, Rbp4, and Ntsr1 neurons (within L4, L5, and L6, respectively) evoked distinct responses in M1 and motor-related subcortical regions, including striatum and motor thalamus. We also found that fMRI responses from targeted stimulations correlated with both local field potentials (LFPs) and spike changes. This study represents a step forward in our understanding of how different layers of primary motor cortex are embedded in brain-wide circuitry.

Methylenetetrahydrofolate reductase deficiency alters cellular response after ischemic stroke in male mice.

Objective: Elevated homocysteine concentrations are a risk factor for stroke. A common genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR 677 C→T) results in elevated levels of homocysteine. MTHFR plays a critical role in the synthesis of S-adenosylmethionine (SAM), a global methyl donor. Our previous work has demonstrated that Mthfr+/- mice, which model the MTHFR polymorphism in humans, are more vulnerable to ischemic damage. The aim of this study was to investigate the cellular mechanisms by which the MTHFR-deficiency changes the brain in the context of ischemic stroke injury.Methods: In the present study, three-month-old male Mthfr+/- and wild-type littermate mice were subjected to photothrombosis (PT) damage. Four weeks after PT damage, animals were tested on behavioral tasks, in vivo imaging was performed using T2-weighted MRI, and brain tissue was collected for histological analysis.Results: Mthfr+/- animals used their non-impaired forepaw more to explore the cylinder and had a larger damage volume compared to wild-type littermates. In brain tissue of Mthfr+/- mice methionine adenosyltransferase II alpha (MAT2A) protein levels were decreased within the damage hemisphere and increased levels in hypoxia-induced factor 1 alpha (HIF-1α) in non-damage hemisphere. There was an increased antioxidant response in the damage site as indicated by higher levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in neurons and astrocytes and neuronal superoxide dismutase 2 (SOD2) levels.Conclusions: Our results suggest that Mthfr+/- mice are more vulnerable to PT-induced stroke damage through the regulation of the cellular response. The increased antioxidant response we observed may be compensatory to the damage amount.

Influence of metabolic syndrome on cerebral perfusion and cognition.

Vascular cognitive impairment (VCI) is associated with chronic cerebral hypoperfusion (CCH) and memory deficits, and often occurs concurrently with metabolic syndrome (MetS). Despite their common occurrence, it is unknown whether CCH and MetS act synergistically to exacerbate VCI-associated pathology. Here, using male Sprague-Dawley rats, we examined the effects of a clinically relevant model of adolescent-onset MetS and adult-onset CCH on neuro-vascular outcomes, combining a cafeteria diet with a 2-vessel occlusion (2VO) model. Using longitudinal imaging, histology, and behavioural assessments, we identified several features of MetS and CCH including reduced cerebral blood volume, white matter atrophy, alterations in hippocampal cell density, and memory impairment. Furthermore, we identified a number of significant associations, potentially predictive of MetS and pathophysiological outcomes. White matter volume was positively correlated to HDL cholesterol; hippocampal cell density was negatively correlated to fasted blood glucose; cerebral blood flow and volume was negatively predicted by the combination of 2VO surgery and increased fasted blood glucose. These results emphasize the importance of including comorbid conditions when modeling VCI, and they outline a highly translational preclinical model that could be used to investigate potential interventions to mitigate VCI-associated pathology and cognitive decline.

Prospective comparative diagnostic accuracy evaluation of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) MR perfusion in differentiating tumor recurrence from radiation necrosis in treated high-grade gliomas.

BACKGROUND: The appearance of a new enhancing lesion after surgery and chemoradiation for high-grade glioma (HGG) presents a common diagnostic dilemma. Histopathological analysis remains the reference standard in this situation. PURPOSE: To prospectively compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) in differentiating tumor recurrence (TR) from radiation necrosis (RN). STUDY TYPE: Prospective diagnostic accuracy study. POPULATION: In all, 98 consecutive treated HGG patients with new enhancing lesion. We excluded 32 patients due to inadequate follow-up or technical limitation. FIELD STRENGTH/SEQUENCE: 3 T DCE and DSC MR. ASSESSMENT: Histogram and hot-spot analysis of cerebral blood volume (CBV), corrected CBV, Ktrans , area under the curve (AUC), and plasma volume (Vp). The reference standard of TR and/or RN was determined by histopathology in 43 surgically resected lesions or by clinical/imaging follow-up in the rest. STATISTICAL TESTS: Mann-Whitney U-tests, receiver operating characteristic (ROC) curve, and logistic regression analysis. RESULTS: A total of 68 lesions were included. There were 37 TR, 28 RN, and three lesions with equal proportions of TR and RN. TR had significantly higher CBV, corrected CBV, CBV ratio, corrected CBV ratio, AUC ratio, and Vp ratio (P < 0.05) than RN on hot-spot analysis. CBV had the highest diagnostic accuracy (AUROC 0.71). On histogram analysis, TR had higher CBV and corrected CBV maximal value compared with RN (P = 0.006, AUROC = 0.70). Only CBV on hot-spot analysis remained significant after correction for multiple comparison, with no significant improvement in diagnostic accuracy when using a combination of parameters (AUROC 0.71 vs. 0.76, P = 0.24). DATA CONCLUSION: DSC-derived CBV is the most accurate perfusion parameter in differentiating TR and RN. DSC and DCE-derived parameters reflecting the blood volume in an enhancing lesion are more accurate than the DCE-derived parameter Ktrans . Clinical practice may be best guided by blood volume measurements, rather than permeability assessment for differentiation of TR from RN. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:573-582.

Imaging of the rabbit supraspinatus enthesis at 7 Tesla: a 4-week time course after repair surgery and effect of channeling.

PURPOSE: To image the supraspinatus enthesis reformation of rabbit shoulders by magnetic resonance at 7 Tesla (T) using T2 mapping after surgical repair and to assess the effects of channeling aimed at enhancing enthesis reformation. MATERIALS AND METHODS: In 112 rabbits, the distal supraspinatus (SSP) tendon was unilaterally detached and reattached after 1 week. At the first surgery, channeling was performed at the footprint in 64 rabbits. At the second surgery, the SSP tendon of all rabbits was re-attached to the greater tuberosity. The shoulders were harvested at 0, 1, 2, or 4 weeks after the repair surgery and were imaged at 7T. Quantitative T2 mapping was performed using multi slice two-dimensional multi-echo spin-echo sequence with fat saturation. Enthesis regions of interests were drawn on three slices at the footprint to measure T2 relaxation times. RESULTS: Tendon repair (F(2, 218) = 44; P < 2.2e-16) and postoperative duration (F(3, 218) = 4.8; P = 0.006) both affected significantly the T2 values while channeling had no significant effect. For the time effect, the only pair with a statistical difference was the 0-week and 4-week for the channeling groups (P = 0.023). CONCLUSION: Enthesis reformation early after surgical repair of the SSP distal tendon was characterized by increasing T2 values. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:461-467.

Holocranohistochemistry enables the visualization of α-synuclein expression in the murine olfactory system and discovery of its systemic anti-microbial effects.

Braak and Del Tredici have proposed that typical Parkinson disease (PD) has its origins in the olfactory bulb and gastrointestinal tract. However, the role of the olfactory system has insufficiently been explored in the pathogeneses of PD and Alzheimer disease (AD) in laboratory models. Here, we demonstrate applications of a new method to process mouse heads for microscopy by sectioning, mounting, and staining whole skulls ('holocranohistochemistry'). This technique permits the visualization of the olfactory system from the nasal cavity to mitral cells and dopamine-producing interneurons of glomeruli in the olfactory bulb. We applied this method to two specific goals: first, to visualize PD- and AD-linked gene expression in the olfactory system, where we detected abundant, endogenous α-synuclein and tau expression in the olfactory epithelium. Furthermore, we observed amyloid-ß plaques and proteinase-K-resistant α-synuclein species, respectively, in cranial nerve-I of APP- and human SNCA-over-expressing mice. The second application of the technique was to the modeling of gene-environment interactions in the nasal cavity of mice. We tracked the infection of a neurotropic respiratory-enteric-orphan virus from the nose pad into cranial nerves-I (and -V) and monitored the ensuing brain infection. Given its abundance in the olfactory epithelia, we questioned whether α-synuclein played a role in innate host defenses to modify the outcome of infections. Indeed, Snca-null mice were more likely to succumb to viral encephalitis versus their wild-type littermates. Moreover, using a bacterial sepsis model, Snca-null mice were less able to control infection after intravenous inoculation with Salmonella typhimurium. Together, holocranohistochemistry enabled new discoveries related to α-synuclein expression and its function in mice. Future studies will address: the role of Mapt and mutant SNCA alleles in infection paradigms; the contribution of xenobiotics in the initiation of idiopathic PD; and the safety to the host when systemically targeting α-synuclein by immunotherapy.

The SIRT1 deacetylase protects mice against the symptoms of metabolic syndrome.

Type 2 diabetes, hepatic steatosis, and gut dysbiosis are pathophysiological consequences of obesity. Sirtuin (SIRT)-1 is a protein deacetylase implicated in the regulation of metabolic activity. We set out to determine whether the catalytic activity of SIRT1 plays a role in the development of metabolic syndrome, hepatic steatosis, and the distribution of gut microbiota. We challenged with a high-fat diet (HFD) a strain of mice homozygous for a Sirt1 allele carrying a point mutation that ablates the deacetylase activity of SIRT1. When compared to wild-type animals, mice lacking SIRT1 catalytic activity rapidly accumulated excessive hepatic lipid while fed the HFD, an effect evident within 2 wk of HFD feeding. Both white and brown adipose depots became hypertrophic, and the animals developed insulin resistance. The ratio of the major phyla of gut microbiota (Firmicutes and Bacteroidetes) increased rapidly in the SIRT1-deficient mice after HFD challenge. We conclude that the deacetylase activity of SIRT1 plays an important role in regulating glucose and hepatic lipid homeostasis. In addition, the composition of gut microbiota is influenced by both the animals' Sirt1 genotype and diet composition.

Longitudinal Brain Perfusion and Symptom Presentation Following Pediatric Concussion: A Pediatric Concussion Assessment of Rest and Exertion+MRI (PedCARE+MRI) Substudy.

Emerging evidence suggests that advanced neuroimaging modalities such as arterial spin labelling (ASL) might have prognostic utility for pediatric concussion. This study aimed to: 1) examine group differences in global and regional brain perfusion in youth with concussion or orthopedic injury (OI) at 72 h and 4 weeks post-injury; 2) examine patterns of abnormal brain perfusion within both groups and their recovery; 3) investigate the association between perfusion and symptom burden within concussed and OI youths at both time-points; and 4) explore perfusion between symptomatic and asymptomatic concussed and OI youths. Youths ages 10.00-17.99 years presenting to the emergency department with an acute concussion or OI were enrolled. ASL-magnetic resonance imaging scans were conducted at 72 h and 4 weeks post-injury to measure brain perfusion, along with completion of the Health Behavior Inventory (HBI) to measure symptoms. Abnormal perfusion clusters were identified using voxel-based z-score analysis at each visit. First, mixed analyses of covariance (ANCOVAs) investigated the Group*Time interaction on global and regional perfusion. Post hoc region of interest (ROI) analyses were performed on significant regions. Second, within-group generalized estimating equations investigated the recovery of abnormal perfusion at an individual level. Third, multiple regressions at each time-point examined the association between HBI and regional perfusion, and between HBI and abnormal perfusion volumes within the concussion group. Fourth, whole-brain one-way ANCOVAs explored differences in regional and abnormal perfusion based on symptomatic status (symptomatic vs. asymptomatic) and OIs at each time-point. A total of 70 youths with a concussion [median age (interquartile range; IQR) = 12.70 (11.67-14.35), 47.1% female] and 29 with an OI [median age (IQR) = 12.05 (11.18-13.89), 41.4% female] were included. Although no Group effect was found in global perfusion, the concussion group showed greater adjusted perfusion within the anterior cingulate cortex/middle frontal gyrus (MFG) and right MFG compared with the OI group across time-points (ps ≤ 0.004). The concussion group showed lower perfusion within the right superior temporal gyrus at both time-points and bilateral occipital gyrus at 4 weeks, (ps ≤ 0.006). The number of hypoperfused clusters was increased at 72 h compared with 4 weeks in the concussion youths (p < 0.001), but not in the OIs. Moreover, Group moderated the HBI-perfusion association within the left precuneus and superior frontal gyrus at both time-points, (ps ≤ 0.001). No association was found between HBI and abnormal perfusion volume within the concussion group at any visits. At 4 weeks, the symptomatic sub-group (n = 10) showed lower adjusted perfusion within the right cerebellum and lingual gyrus, while the asymptomatic sub-group (n = 59) showed lower adjusted perfusion within the left calcarine, but greater perfusion within the left medial orbitofrontal cortex, right middle frontal gyrus, and bilateral caudate compared with OIs. Yet, no group differences were observed in the number of abnormal perfusion clusters or volumes at any visit. The present study suggests that symptoms may be associated with changes in regional perfusion, but not abnormal perfusion levels.

Fibrinogen aptamer functionalized gold-coated iron-oxide nanoparticles for targeted imaging of thrombi.

Targeting of molecular constituents of thrombi with aptamer functionalized core-shell nanoparticles (CSN) allowed for high resolution clot delineation in T2-weighted magnetic resonance imaging. Meanwhile, the gold-coating demonstrated sufficient contrast capabilities in computed tomography (1697 HU µM-1). This targeted CSN formulation could allow for precise imaging of blood clots at low nanomolar concentrations.

Repeated hippocampal seizures lead to brain-wide reorganization of circuits and seizure propagation pathways.

Repeated seizure activity can lead to long-term changes in seizure dynamics and behavior. However, resulting changes in brain-wide dynamics remain poorly understood. This is due partly to technical challenges in precise seizure control and in vivo whole-brain mapping of circuit dynamics. Here, we developed an optogenetic kindling model through repeated stimulation of ventral hippocampal CaMKII neurons in adult rats. We then combined fMRI with electrophysiology to track brain-wide circuit dynamics resulting from non-afterdischarge (AD)-generating stimulations and individual convulsive seizures. Kindling induced widespread increases in non-AD-generating stimulation response and ipsilateral functional connectivity and elevated anxiety. Individual seizures in kindled animals showed more significant increases in brain-wide activity and bilateral functional connectivity. Onset time quantification provided evidence for kindled seizure propagation from the ipsilateral to the contralateral hemisphere. Furthermore, a core of slow-migrating hippocampal activity was identified in both non-kindled and kindled seizures, revealing a novel mechanism of seizure sustainment and propagation.

Arterial input functions determined from MR signal magnitude and phase for quantitative dynamic contrast-enhanced MRI in the human pelvis.

Dynamic contrast-enhanced (DCE) MRI is often used to measure the transfer constant (Ktrans) and distribution volume (ve) in pelvic tumors. For optimal accuracy and reproducibility, one must quantify the arterial input function (AIF). Unfortunately, this is challenging due to inflow and signal saturation. A potential solution is to use MR signal phase (ϕ), which is relatively unaffected by these factors. We hypothesized that phase-derived AIFs (AIFϕ) would provide more reproducible Ktrans and ve values than magnitude-derived AIFs (AIF|S|). We tested this in 27 prostate dynamic contrast-enhanced MRI studies (echo time=2.56 ms, temporal resolution=13.5 s), using muscle as a standard. AIFϕ peak amplitude varied much less as a function of measurement location (inferior-superior) than AIF|S| (5.6±0.6 mM vs. 2.6±1.5 mM), likely as a result of ϕ inflow insensitivity. However, our main hypothesis was not confirmed. The best AIF|S| provided similar reproducibility versus AIFϕ (interpatient muscle Ktrans=0.039±0.021 min(-1) vs. 0.037±0.025 min(-1), ve=0.090±0.041 vs. 0.062±0.022, respectively).

Exploring the Unique Contrast Properties of Aptamer-Gadolinium Conjugates in Magnetic Resonance Imaging for Targeted Imaging of Thrombi.

Objective: An important clinical question in the determination of the extent of thrombosis-related vascular conditions is the identification of blood clot location. Fibrin is a major molecular constituent of blood clots and can, therefore, be utilized in molecular imaging. In this proof-of-concept study, we sought to prepare a fibrin-targeting magnetic resonance imaging contrast agent, using a Gd(III)-loaded fibrinogen aptamer (FA) chelate conjugate (Gd(III)-NOTA-FA) (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid), to endow the ability to specifically accumulate at the location of blood clots, thereby enhancing contrast capabilities. Methods: The binding affinity of FA for fibrin was confirmed by fluorescence microscopy and microscale thermophoresis. The preparation and effective loading of the chelate-aptamer conjugates were confirmed by mass spectrometry and a xylenol orange colorimetric test. Longitudinal and transverse relaxivities and the effects of target binding were assessed using T1- and T2-map sequences at 7 T. T1- and T2-weighted images were acquired after blood clots were treated with Gd(III)-NOTA-FA. Collagen was used as the protein control, while an unrelated aptamer sequence, FB139, was used as the aptamer control. Results: FA demonstrated a high affinity and selectivity toward the polymeric protein, with a Kd of 16.6 nM, confirming an avidity over fibrinogen. The longitudinal (r1) and transverse (r2) relaxivities of Gd(III)-NOTA-FA demonstrated that conjugation to the long aptamer strand shortened T1 relaxation times and increased T2 relaxation times (3.04 and 38.7 mM-1 s-1, respectively). These effects were amplified by binding to the fibrin target (1.73 and 46.5 mM-1 s-1, respectively). In vitro studies with thrombin-polymerized human blood (clots) in whole blood showed an unexpected enhancement of signal intensity (hyperintense) produced exclusively at the location of the clot during the T2-weighted scan, while the presence of fibrinogen within a whole blood pool resulted in T1 signal intensity enhancement throughout the pool. This is advantageous, as simply reversing the type of a scan from a typical T1-weighted to a T2-weighted would allow to selectively highlight the location of blood clots. Conclusions: Gd(III)-NOTA-FA can be used for molecular imaging of thrombi, through fibrin-targeted delivery of contrast to the location of blood clots in T2-weighted scans.

Quantitative analysis of repaired rabbit supraspinatus tendons (± channeling) using magnetic resonance imaging at 7 Tesla.

BACKGROUND: The quantitative assessment of supraspinatus tendons by conventional magnetic resonance is limited by low contrast-to-noise ratio (CNR). Magnetic resonance imaging (MRI) scanners operating at 7 Tesla offer high signal-to noise ratio (SNR), low CNR and high spatial resolution that are well-suited for rapidly relaxing tissues like tendons. Few studies have applied T2 and T2* mapping to musculoskeletal imaging and to the rotator cuff tendons. Our objective was to analyze the T2 and T2* relaxation times from surgically repaired supraspinatus tendons and the effect of bone channeling. METHODS: One supraspinatus tendon of 112 adult female New Zealand white rabbits was surgically detached and repaired one week later. Rabbits were randomly assigned to channeling (n=64) or control (n=48) groups and harvested at 0, 1, 2, and 4 weeks. A 7T magnet was used for signal acquisition. For T2 mapping, a sagittal multi slice 2D multi-echo spin-echo (MESE) CPMG sequence with fat saturation was applied and T2* mapping was performed using a 3D UTE sequence. Magnetic resonance images from supraspinatus tendons were analyzed by two raters. Three regions of interest were manually drawn on the first T2-weighted dataset. For T2 and T2*, different ROI masks were generated to obtain relaxation times. RESULTS: T2-weighted maps but not T2*-weighted maps generated reliable signals for relaxation time measurement. Torn supraspinatus tendons had lower T2 than controls at the time of repair (20.0±3.4 vs. 25.6±3.9 ms; P<0.05). T2 increased at 1, 2 and 4 postoperative weeks: 22.7±3.1, 23.3±3.9 and 24.0±5.1 ms, respectively, and values were significantly different from contralateral supraspinatus tendons (24.8±3.1; 26.8±4.3 and 26.5±3.6 ms; all P<0.05). Bone channeling did not affect T2 (P>0.05). CONCLUSIONS: Supraspinatus tendons detached for 1 week had shorter T2 relaxation time compared to contralateral as measured with 7T MRI.

Intracranial Displacement Measurements Within Targeted Anatomical Regions of a Postmortem Human Surrogate Brain Subjected to Impact.

The dynamic response of the human brain subjected to impulsive loading conditions is of fundamental importance to the understanding of traumatic brain injuries. Due to the complexity of such measurements, the existing experimental datasets available to researchers are sparse. However, these measurements are used extensively in the validation of complex finite element models used in the design of protective equipment and the development of injury mitigation strategies. The primary objective of this study was to develop a comprehensive methodology to measure displacement in specific anatomical regions of the brain. A state-of-the-art high-speed cineradiography system was used to capture brain motion in post-mortem human surrogate specimens at a rate of 7500 fps. This paper describes the methodology used to capture these data and presents measurements from these tests. Two-dimensional displacement fields are presented and analyzed based on anatomical regions of the brain. These data demonstrated a multi-modal displacement response in several regions of the brain. The full response of the brain consisted of an elastic superposition of a series of bulk rotations of the brain about its centre of gravity. The displacement field could be linked directly to specific anatomical regions. The methods presented mark an improvement in temporal and spatial resolution of data collection, which has implications for our developing understanding of brain trauma.

Determination of the venous output function from MR signal phase: feasibility for quantitative DCE-MRI in human brain.

For dynamic contrast-enhanced MRI studies in the human brain, it is useful to measure the venous output function (VOF). The purpose of this work was to explore the feasibility of measuring the VOF using the MR signal phase (in absolute units of gadolinium concentration) in the superior sagittal sinus. Phantom experiments were performed to validate the technique for different superior sagittal sinus angles (theta = 0-48 degrees relative to the main magnetic field), different curvatures (straight or radius = 45 mm), and different spatial resolutions (2.2-5.5 mm, to study partial-volume effects). Additionally, the technique was tested on three patients. The phantom experimental results (echo time = 5.5 ms, theta

Imaging cognitive fatigability in multiple sclerosis: objective quantification of cerebral blood flow during a task of sustained attention using ASL perfusion fMRI.

Cognitive fatigability (CF) can be defined as an inability to maintain performance throughout a sustained cognitive task. Individuals with multiple sclerosis (MS) are more susceptible to CF than healthy controls (HCs); however, the neural correlates underlying CF are still under investigation. Arterial spin labeling (ASL) perfusion imaging provides a non-invasive method of objectively quantifying cerebral blood flow (CBF) during sustained attention tasks. To date, no study has yet evaluated CF in MS using this methodology. 10 MS and 10 HCs completed a 20-min psychomotor vigilance task (PVT). CF was evaluated by dividing the PVT into quintiles and examining performance from the 1st to the last. Mean reaction times (RTs) and number of lapses were recorded. Global and regional CBF changes were evaluated throughout the PVT as well as during pre- and post-task rest. Increased susceptibility to CF was noted in the MS group. Distinct patterns of CBF activation were observed in areas comprising fronto-parietal, cortico-striatal, cerebellar, and basal ganglia regions; however, when and how these regions were engaged differed between the MS and HC groups. In particular, dysfunction in CBF to the middle frontal gyrus may underlie the CF effects observed. In addition, individuals with MS appear to struggle with "switching off" regions of the attentional network at rest following sustained cognitive effort. Findings support the use of ASL as an appropriate methodology for evaluating CF in MS with an overall pattern of attentional network dysfunction being observed. Objectively quantifying CF in this manner can help validate patients' subjective complaints.

Rapid monitoring of oxygenation by 19F magnetic resonance imaging: Simultaneous comparison with fluorescence quenching.

The aim of this study was to develop an MRI fluorocarbon oximetry technique using snapshot inversion recovery and compare it with fluorescence quenching fiber-optic probe oximetry (OxyLite) performed simultaneously in experimental mouse tumors. The oxygen reporter probe hexafluorobenzene (HFB) was injected directly into the tumors, along with the insertion of the OxyLite probe. Tumor oxygenation (pO(2)) was modified using carbogen or lethal doses of the anesthetic gas. MRI pO(2) maps were generated in 1.5 min with an in-plane spatial resolution of 1.88 mm. MRI and OxyLite showed consistent baseline and postmortem pO(2) values. Increases in tumor pO(2) during carbogen breathing showed similar kinetics for the two methods. The pO(2) values observed using the OxyLite corresponded with relatively hypoxic values observed by MRI. The apparent discrepancy between mean values might be due to the difference in sampling volumes of the techniques and the observation of multiple locations using (19)F MRI versus a single location using the large optical fiber. Overall, the present method provides a rapid way to map the tumor oxygenation and is particularly suitable to monitor acute changes of pO(2) in tumors.

Cubic versus hexagonal - effect of host crystallinity on the T1 shortening behaviour of NaGdF4 nanoparticles.

Sodium gadolinium fluoride (NaGdF4) nanoparticles are promising candidates as T1 shortening magnetic resonance imaging (MRI) contrast agents due to the paramagnetic properties of the Gd3+ ion. Effects of size and surface modification of these nanoparticles on proton relaxation times have been widely studied. However, to date, there has been no report on how T1 relaxivity (r1) is affected by the different polymorphs in which NaGdF4 crystallizes: cubic (α) and hexagonal (ß). Here, a microwave-assisted thermal decomposition method was developed that grants selective access to NaGdF4 nanoparticles of either phase in the same size range, allowing the influence of host crystallinity on r1 to be investigated. It was found that at 3 T cubic NaGdF4 nanoparticles exhibit larger r1 values than their hexagonal analogues. This result was interpreted based on Solomon-Bloembergen-Morgan theory, suggesting that the inner sphere contribution to r1 is more pronounced for cubic NaGdF4 nanoparticles as compared to their hexagonal counterparts. This holds true irrespective of the chosen surface modification, i.e. small citrate groups or longer chain poly(acrylic acid). Key aspects were found to be a polymorph-induced larger hydrodynamic diameter and the higher magnetization possessed by cubic nanoparticles.

Lateral Trochlear Ridge: A Non-Articulating Zone for Anterior-to-Posterior Screw Placement in Fractures Involving the Capitellum and Trochlea.

BACKGROUND: Coronal shear fractures of the distal aspect of the humerus that involve the capitellum and the trochlea are rare; nevertheless, they are difficult to treat because of the complex fracture patterns and osteochondral nature of the fragments, limiting optimal screw placement. The use of anterior-to-posterior screw fixation by a lag technique (without countersinking) could potentially improve the strength of the construct. Our primary research question was to anatomically determine if there is a non-articulating zone for screw placement along the anterior aspect of the lateral trochlear ridge (aLTR) throughout normal elbow range of motion. METHODS: Eight fresh-frozen cadaveric elbows were used. The region of interest was defined with 3 polymeric pins inserted in the inferior, middle, and superior-most aspects of the aLTR of each elbow, with use of an extensor digitorum communis (EDC) split approach. The elbows were then mounted on a magnetic resonance imaging (MRI)-compatible compression frame and subjected to high-resolution 7-T MRI at 90°, 120°, and 145° of flexion (positions of potential impingement), and at neutral and maximal pronation and maximal supination for each position of flexion. Portions of the aLTR that had free adjacent space were identified using the sagittal and coronal scans. This non-articulating region was identified as the "non-articulating zone" (NAZ). RESULTS: The NAZ was found to encompass the proximal 38.2% (range, 30.2% to 48.9%) of the aLTR, measuring, on average, 5.2 mm in width. It was consistently located either directly adjacent to the apex of the ridge or just medial to it. The distal 61.8% of the aLTR articulated with either the ulna or the radial head in some of the elbows. CONCLUSIONS: Our results suggest that there is a portion of the aLTR that, despite being covered with articular cartilage, is non-articulating throughout normal elbow range of motion. CLINICAL RELEVANCE: In situations in which headless anterior-to-posterior and posterior-to-anterior screw insertion results in inadequate fixation of capitellar-trochlear fractures, anterior-to-posterior lag screw instrumentation along the non-articulating portion of the aLTR may provide a location for additional fixation in some patients. However, because of variation between patients, each case must be individualized.