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Aim: To propose a new multimodal imaging agent targeting amyloid-β (Aβ) plaques in Alzheimer’s disease. Materials & methods: A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimer’s disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Results & conclusion: Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. In vivo brain uptake was dependent on the blood–brain barrier status. Nevertheless, multimodal imaging showed successful Aβ targeting in both transgenic mice and Aβ fibril-injected rats.

Two mononuclear ferric complexes are reported that respond to a pH change with a 27- and 71-fold jump, respectively, in their capacity to accelerate the longitudinal relaxation rate of water-hydrogen nuclei, and this starting from a negligible base value of only 0.06. This unprecedented performance bodes well for tackling the sensitivity issues hampering the development of Molecular MRI. The two chelates also excel in the fully reversible and fatigue-less nature of this phenomenon. The structural reasons for this performance reside in the macrocyclic nature of the hexa-dentate ligand, as well as the presence of a single pendant arm displaying a five-membered lactam or carbamate which show (perturbed) pKa values of 3.5 in the context of this N6⟺N5O1 coordination motif.

Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t-MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal-level data from three experimental series were combined in a study population of 104 t-MCAO rats (45 in HDT15 group and 59 in flat position group). Co-primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non-ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm

Background Hemophilia is characterized by a compromised hemostatic response with delayed development of a clot and the formation of clots that are vulnerable to fibrinolysis. We proposed to study, in vitro and in factor VIII knockout mice (FVIII-KO), whether hemostasis is improved with the addition of tranexamic acid (TXA) to low FVIII plasma concentrations. Methods In vitro, blood samples from adults with severe hemophilia-A, spiked to final concentrations of 0-3-10 and 30IU.dL-1 of FVIII, were studied with and without TXA 0.1 mg/mL using thromboelastography in the presence of tPA (ROTEM-tPA), thrombin generation (TG) assay, and scanning electron microscopy. FVIII-KO mice received prophylaxis before trauma, to obtain circulating plasma FVIII at 3 IU.dL-1 or FVIII 3IU.dL-1 + TXA 0.1 mg/mL. After trauma-induced knee joint bleeding, magnetic resonance imaging, histological analysis, and tail clip assay were used to compare hemostastic efficacy of the two prophylactic strategies. Results A dose-dependent improvement of TG was observed with recombinant FVIII (rFVIII) alone (P = .024). As expected, no effect of TXA on TG capacity was observed. Fibrin fiber diameters were significantly decreased with TXA + rFVIII compared to rFVIII, suggesting a stronger fibrin network. Surprisingly, ROTEM-tPA was normalized with TXA alone. In FVIII-KO mice, blood loss after tail clip was lower after prophylaxis with rFVIII + TXA compared to rFVIII, with no statistical significance (P = .15). However, MRI results and histological analysis of knee joints showed that the addition of TXA significantly decreased joint bleeding (P = .022). Conclusion Our results suggest a potential benefit of TXA when used in combination with FVIII in prophylactic settings.

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce StandardRat, a consensus rat functional MRI acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired in rats from 46 centers. We developed a reproducible pipeline for the analysis of rat data acquired with diverse protocols and determined experimental and processing parameters associated with a more robust functional connectivity detection. We show that the standardized protocol enhances biologically plausible functional connectivity patterns, relative to pre-existing acquisitions. The protocol and processing pipeline described here are openly shared with the neuroimaging community to promote interoperability and cooperation towards tackling the most important challenges in neuroscience.

International audience; Uncertainty exists regarding whether cyclophilin D (CypD), a mitochondrial matrix protein that plays a key role in ischemia-reperfusion injury, can be a pharmacological target for improving outcomes after cardiac arrest (CA), especially when therapeutic hypothermia is used. Using CypD knockout mice (CypD−/−), we investigated the effects of loss of CypD on short-term and medium-term outcomes after CA. CypD−/− mice or their wild-type (WT) littermates underwent either 5-minute CA followed by resuscitation with/without hypothermia at 33-34 C (targeted temperature reached within minutes after resuscitation), or a sham procedure. Brain and cardiac injury were assessed using echocardiography, neurological scores, MRI and biomarkers. Seven-day survival was compared using Kaplan-Meier estimates. The rate of restoration of spontaneous circulation was significantly higher in CypD−/− mice (with shorter cardiac massage duration) than in WT mice (p

With the aim of designing a preclinical study evaluating an intracerebral cell-based therapy for stroke, an observational study was performed in the rat suture model of ischemic stroke. Objectives were threefold: (i) to characterize neurofunctional and imaging readouts in the first weeks following transient ischemic stroke, according to lesion subtype (hypothalamic, striatal, corticostriatal); (ii) to confirm that intracerebral administration does not negatively impact these readouts; and (iii) to calculate sample sizes for a future therapeutic trial using these readouts as endpoints. Our results suggested that the most relevant endpoints were side bias (staircase test) and axial diffusivity (AD) (diffusion tensor imaging). Hypothalamic-only lesions did not affect those parameters, which were close to normal. Side bias in striatal lesions reached near-normal levels within 2 weeks, while rats with corticostriatal lesions remained impaired until week 14. AD values were decreased at 4 days and increased at 5 weeks post-surgery, with a subtype gradient: hypothalamic < striatal < corticostriatal. Intracerebral administration did not impact these readouts. After sample size calculation (18-147 rats per group according to the endpoint considered), we conclude that a therapeutic trial based on both readouts would be feasible only in the framework of a multicenter trial.

Background and Purpose: Currently, reperfusion is the only existing treatment strategy for patients with acute ischemic stroke. However, reperfusion may cause further brain damage. One of the feasible therapies targeting reperfusion injury is remote ischemic conditioning (RIC). The main objective of this study was to test the neuroprotective effects of RIC in a rat model of acute ischemic stroke in a randomized and blinded two-centre MRI study with a priori sample size calculation . Methods: Eighty male Sprague Dawley rats underwent 90-min middle cerebral artery occlusion. Multiparametric MRI was performed per-occlusion to ascertain focal cerebral ischemia (inclusion criteria) and to control interindividual variability in the analysis. RIC was started 10 min before reperfusion, and consisted of 4 cycles of 5-min left hind limb ischemia. The primary endpoint of the study was infarct size measured on T2-weighted MRI at 24h, corrected for edema, and expressed as percentage of the area-at-risk of infarction . Secondary endpoints were hemispheric space-modifying edema, infarct growth between per-occlusion and 24h MRI, and neurofunctional outcome measured by neuroscores. Results: Two animals died in each group. In total, 47 rats were included in the analysis after applying the pre-defined inclusion criteria (23 in control group and 24 in RIC group). Infarct size was significantly reduced in the RIC group (mean, interquartile range: 19% [8% ; 32%] vs control: 40% [17% ; 59%], p=0.028). This infarct-limiting effect was still statistically significant after adjustment for apparent diffusion coefficient (ADC) lesion size in multivariate analysis. In the subgroup of rats with ADC lesion > 100 mm3, infarct size reduced from 58% [40%; 66%] to 32% [27%; 40%], p=0.004. In line with this result, RIC significantly improved neuroscores (6 [3 ; 8] vs control: 9 [7 ; 11], p=0.032). The other secondary endpoints were not statistically different between groups. Conclusions: RIC in the setting of acute stroke in rats is safe, reduces infarct size and improves functional recovery in a two-centre international study using translational imaging endpoints.

Reperfusion is the only existing strategy for patients with acute ischemic stroke, however it causes further brain damage itself. A feasible therapy targeting reperfusion injury is remote ischemic conditioning (RIC). This was a two-centre, randomized, blinded international study, using translational imaging endpoints, aimed to examine the neuroprotective effects of RIC in ischemic stroke model. 80 male rats underwent 90-min middle cerebral artery occlusion. RIC consisted of 4 × 5 min cycles of left hind limb ischemia. The primary endpoint was infarct size measured on T2-weighted MRI at 24 h, expressed as percentage of the area-at-risk. Secondary endpoints were: hemispheric space-modifying edema, infarct growth between per-occlusion and 24 h MRI, neurofunctional outcome measured by neuroscores. 47 rats were included in the analysis after applying pre-defined inclusion criteria. RIC significantly reduced infarct size (median, interquartile range: 19% [8%; 32%] vs control: 40% [17%; 59%], p = 0.028). This effect was still significant after adjustment for apparent diffusion coefficient lesion size in multivariate analysis. RIC also improved neuroscores (6 [3; 8] vs control: 9 [7; 11], p = 0.032). Other secondary endpoints were not statistically different between groups. We conclude that RIC in the setting of acute ischemic stroke in rats is safe, reduces infarct size and improves functional recovery.

The emerging concept of "biased agonism" denotes the phenomenon whereby agonists can preferentially direct receptor signalling to specific intracellular responses among the different transduction pathways, thus potentially avoiding side effects and improving therapeutic effects. The aim of this study was to investigate biased agonism by using pharmacological magnetic resonance imaging (phMRI). The cerebral blood oxygen level dependent (BOLD) signal changes induced by increasing doses of two serotonin 5-HT1A receptor biased agonists, NLX-112 and NLX-101, were mapped in anaesthetized rats. Although both compounds display high affinity, selectivity and agonist efficacy for 5-HT1A receptors, NLX-101 is known to preferentially activate post-synaptic receptors, whereas NLX-112 targets both pre- and post-synaptic receptors. We used several doses of agonists in order to determine if the regional selectivity of NLX-101 was dose-dependent. NLX-112 and NLX-101 induced different positive and negative hemodynamic changes patterns at equal doses. Importantly, NLX-101 had no significant effect in regions expressing pre-synaptic receptors contrary to NLX-112. NLX-112 also produced higher BOLD changes than NLX-101 in the orbital cortex, the somatosensory cortex, and the magnocellular preoptic nuclei. In other regions such as the retrosplenial cortex and the dorsal thalamus, the drugs had similar effects. In terms of functional connectivity, NLX-112 induced more widespread changes than NLX-101. The present phMRI study demonstrates that two closely-related agonists display notable differences in their hemodynamic "fingerprints". These data support the concept of biased agonism at 5-HT1A receptors and raise the prospect of identifying novel therapeutics which exhibit improved targeting of brain regions implicated in neuropsychiatric disorders. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

The emerging concept of "biased agonism" denotes the phenomenon whereby agonists can preferentially direct receptor signalling to specific intracellular responses among the different transduction pathways, thus potentially avoiding side effects and improving therapeutic effects. The aim of this study was to investigate biased agonism by using pharmacological magnetic resonance imaging (phMRI). The cerebral blood oxygen level dependent (BOLD) signal changes induced by increasing doses of two serotonin 5-HT

Inflammation may play a role in the development of epilepsy after brain insults. [11C]-( R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [11C]-( R)-PK11195 binding during epileptogenesis after pilocarpine-induced status epilepticus (SE), a model of temporal lobe epilepsy. Nine male rats were studied thrice (D0-1, D0 + 6, D0 + 35, D0 = SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/CT. On D0 + 35, femoral arterial blood was sampled for rat-specific metabolite-corrected arterial plasma input functions (AIFs). In multiple MR-derived ROIs, we assessed four kinetic models (two with AIFs; two using a reference region), standard uptake values (SUVs), and a model with a mean AIF. All models showed large (up to two-fold) and significant TSPO binding increases in regions expected to be affected, and comparatively little change in the brainstem, at D0 + 6. Some individuals showed increases at D0 + 35. AIF models yielded more consistent increases at D0 + 6. FA values were decreased at D0 + 6 and had recovered by D0 + 35. MD was increased at D0 + 6 and more so at D0 + 35. [11C]-( R)-PK11195 PET binding and MR biomarker changes could be detected with only nine rats, highlighting the potential of longitudinal imaging studies.

To assess spatiotemporal brain infarction evolution by sequential multimodal magnetic resonance (MR) imaging in an endovascular model of acute stroke in rats. A microwire was selectively placed in the middle cerebral artery (MCA) in 16 consecutives rats during 90 minutes occlusion. Longitudinal 7-T MR imaging, including angiography, diffusion, and perfusion was performed during ischemia, immediately after reperfusion, 3 h and 24 h after subsequent reperfusion. MCA occlusion was complete in 75 % and partial in 18.7 %. Hypoperfusion (mean ± SD) was observed in all animals during ischemia (-59 ± 18 % of contralateral hemisphere, area 31 ± 5 mm2). Infarction volume (mean ± SD) was 90 ± 64 mm3 during ischemia and 57 ± 67 mm3 at 24 h. Brain infarction was fronto-parietal cortical in five animals (31 %), striatal in four animals (25 %), and cortico-striatal in seven animals (44 %) at 24 h. All rats survived at 24 h. This model is suitable to neuroprotection studies because of possible acute and close characterization of spatiotemporal evolution of brain infarction by MR imaging techniques, and evidence of ischemic penumbra, the target of neuroprotection agents. However, optimization of the brain infarct reproducibility needs further technical and neurointerventional tools improvements. • Nitinol microwire is MRI compatible allowing spatiotemporal characterization of brain infarction in rats. • Microwire selective placement in middle cerebral artery allows complete artery occlusion in 75 %. • A diffusion/perfusion mismatch during arterial occlusion is observed in 77 % of rats.

The observation that amyloid radiotracers developed for Alzheimer’s disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [11C]PIB was used to show thatin vivoPET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such.Ex vivoautoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content.

International audience; Objective: The epilepsy-aphasia spectrum (EAS) is a heterogeneous group of age-dependent childhood disorders characterized by sleep-activated discharges associated with infrequent seizures and language, cognitive, and behavioral deficits. Defects in the GRIN2A gene, encoding a subunit of glutamate-gated N-methyl-D-aspartate (NMDA) receptors, represent the most important cause of EAS identified so far. Neocortical or thalamic lesions were detected in a subset of severe EAS disorders, and more subtle anomalies were reported in patients with so-called "benign" phenotypes. However, whether brain structural alterations exist in the context of GRIN2A defects is unknown. Methods: Magnetic resonance diffusion tensor imaging (MR-DTI) was used to perform longitudinal analysis of the brain at 3 developmental timepoints in living mice genetically knocked out (KO) for Grin2a. In addition, electroencephalogra-phy (EEG) was recorded using multisite extracellular electrodes to characterize the neocortical activity in vivo. Results: Microstructural alterations were detected in the neocortex, the corpus callosum, the hippocampus, and the thalamus of Grin2a KO mice. Most MR-DTI alterations were detected at a specific developmental stage when mice were aged 30 days, but not at earlier (15 days) or later (2 months) ages. EEG analysis detected epileptiform discharges in Grin2a KO mice in the third postnatal week. Significance: Grin2a KO mice replicated several anomalies found in patients with EAS disorders. Transient structural alterations detected by MR-DTI recalled the age-dependent course of EAS disorders, which in humans start during childhood and show variable outcome at the onset of adolescence. Together with the epileptiform discharges detected in young Grin2a KO mice, our data suggested the existence of early anomalies in the maturation of the neocortical and thalamocortical systems. Whereas the possible relationship of those anomalies with sleep warrants further investigations, our data suggest that Grin2a KO mice may serve as an animal model to study the neu-ronal mechanisms of EAS disorders and to design new therapeutic strategies. K E Y W O R D S brain structure, EEG, epilepsy-aphasia, mouse model, MR-DTI Salmi and Bolbos contributed equally to the study.

International audience; Serotonin 1A (5-HT 1A) receptors are involved in several physiological and pathological processes and constitute therefore an important therapeutic target. The recent pharmacological concept of biased agonism asserts that highly selective agonists can preferentially direct receptor signaling to specific intracellular responses, opening the possibility of drugs targeting a receptor subtype in specific brain regions. The present study brings additional support to this concept thanks to functional magnetic resonance imaging (7 Tesla-fMRI) in anaesthetized rats. Three 5-HT 1A receptor agonists (8-OH-DPAT, F13714 and F15599) and one 5-HT 1A receptor antagonist (MPPF) were compared in terms of influence on the brain blood oxygen level-dependent (BOLD) signal. Our study revealed for the first time contrasting BOLD signal patterns of biased agonists in comparison to a classical agonist and a silent antagonist. By providing functional information on the influence of pharmacological activation of 5-HT 1A receptors in specific brain regions, this neuroimaging approach, translatable to the clinic, promises to be useful in exploring the new concept of biased agonism in neuropsychopharmacology. 5-HT 1A receptors belong to the family of serotonin receptors, composed of 13 receptor subtypes. 5-HT 1A receptors are known to play a key role in serotonin neurotransmission due to their localization both as pre-synaptic receptors located on serotonin cell bodies in the raphe nuclei (somatodendritic receptors) and as post-synaptic heteroreceptors in forebrain areas that receive serotonergic projections. In such areas, 5-HT 1A receptors are located on pyramidal and GABAergic neurons of the neocortex and limbic system 1,2. Because of their distribution pattern and of their central role in the modulation of the serotoninergic neurotransmission, 5-HT 1A receptors are involved in several physiological and pathological processes and constitute therefore an important therapeutic target for psychiatric 3 and, more recently, for neurological disorders 4. Indeed, it is now well establish that 5-HT 1A receptors are one of the main targets for the treatment of mood disorders 5 , with different actions that depend strongly on their localization. For example, activation of soma-todendritic receptors by serotonin or 5-HT 1A receptor agonists decreases the firing of serotonin neurons in the raphe, and, consequently decreases its terminal release 6. This decrease is thought to be partially responsible for the delay in onset of the therapeutic action of selective serotonin reuptake inhibitors (SSRI) antidepressants 5. A recent study renewed this concept, showing that expression levels of 5-HT 1A somatodendritic receptors, are critically important for SSRI treatment response by controlling serotoninergic tone 7. On the other hand, the activation of postsynaptic 5-HT 1A receptors seems to be equally important for response to antidepressants 5,8. In a different therapeutic area, 5-HT 1A receptor agonism is also known as an important feature of some atypical antipsychotics including clozapine, aripiprazole, ziprasidone and quetiapine 9–12. Recently, 5-HT 1A receptors have attracted renewed interest as possible targets in neuropharmacology. For example, it was described that blockade of post-synaptic 5-HT 1A receptors, located on pyramidal cells, can improve cognition by enhancing glutamatergic transmission 13. This led to clinical trials using the 5-HT 1A antagonist lecozotan as a procognitive drug in Alzheimer's disease 14,15. Other 5-HT 1A receptor ligands such as sarizotan, buspirone and tandospirone were shown to alleviate dyskinesia in Parkinson's disease patients 16,17. More recently

Introduction Hemophilia is an X linked disorder characterized by an increased tendency to spontaneous bleeding resulting from profound compromise of the hemostatic response with delayed development of a clot and the formation of clots that are vulnerable to fibrinolysis. Optimization of clot stability by adding TXA to low concentrations of factor concentrates may be a way to improve prophylaxis in patients with severe hemophilia (sH) without substantially increasing the cost or the burden of more frequent infusions. Aims We proposed to study whether hemostasis is improved with the addition of TXA to low FVIII plasma concentrations (equivalent to trough levels in prophylactic setting). We specifically studied in vitro the clot stability in patients with sHA; and in vivo the hemostatic response to trauma-induced joint bleed and tail clip in FVIII knock-out (KO) mice. Methods After obtaining informed consent, blood samples of 12 adults with sHA were spiked in vitro to achieve final concentrations (FC) of 0-3-10 and 30 IU/dL of FVIII, then studied with and without TXA at FC 0.1mg/ml. Whole blood (WB) was assessed with ROTEM performed after addition of tPA in 6 patients. Thrombin generation (TG) was measured in plasma (PL) of 6 other patients. Clots obtained from TG were examined under electron microscopy (EM) to evaluate the quality of fibrin clot structure. Diameters of randomly selected 100 fibrin fibers were measured in each clot. In animal studies, 13 FVIII KO mice were given FVIII to a plasma concentration of 3 IU/dL to mimic trough FVIII levels in prophylactic setting; 7 were also infused with TXA (FC 0.1mg/ml). 10 minutes after infusion, joint bleeding was induced by knee puncture using a standardized protocol. 2 days post trauma, MRI was done and the joint bleed (surface of hyper signal into the joint) was compared between the groups with and w/o TXA. 10 other FVIII KO mice were infused with 3 IU/dL rFVIII, of which 5 were also infused with TXA (FC 0.1mg/ml). 10 minutes after infusion, the extremity of the tail was cut at 2mm, and then immersed in pre-heated water-filled tube at 37°C. Blood was collected during 10 minutes. After lysis of erythrocytes, the amount of hemoglobin in collected blood was measured using spectrophotometry; means of optical density (OD) were compared between the 2 groups. Results A dose dependent improvement of TG was observed after adding FVIII alone (p=0.024). As expected, the addition of TXA had no effect on TG capcity. Fibrin fiber diameters were significantly decreased with TXA+FVIII compared to FVIII alone (results shown in fig1), suggesting a stronger fibrin network, as thin fibrin fibers are characteristic of a robust fibrin mesh. Surprisingly, ROTEM was fully normalized after addition of TXA only, with no exogenous FVIII. In FVIII KO mice, the addition of TXA to 3 IU/dL rFVIII significantly decreased joint bleeding compared to 3 IU/dL rFVIII alone (p=0.022) (fig2).With the tail clip experiment, the addition of TXA to 3 IU/dLFVIII showed a trend toward improved bleeding when compared to 3 IU/dLFVIII alone; with means of OD±SEM 0,31±0,19 and 0,94±0,45 respectively, but did not reach statistical significance (p=0,15) (fig3). Conclusion Our in vitro and in vivo results suggest a potential benefit of TXA when used in combination with FVIII in prophylactic setting. Disclosures No relevant conflicts of interest to declare.

SummaryObjectiveThe purpose of this study was to evaluate meniscal degeneration in healthy subjects and subjects with osteoarthritis (OA) using T1ρ and T2 measurements and to examine the interrelationship between cartilage and meniscus abnormalities.MethodsQuantitative assessment of cartilage and meniscus was performed using 3T Magnetic Resonance Imaging (MRI) with a T1ρ and T2 mapping technique in 19 controls and 44 OA patients. A sagittal T2-weighted fast spin echo (FSE) fat-saturated image was acquired for cartilage and meniscal Whole-Organ Magnetic Resonance Imaging Score (WORMS) assessment. Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores were obtained to assess clinical symptoms.ResultsThe posterior horn of the medial meniscus (PHMED) had the highest incidence of degeneration. Stratifying subjects on the basis of PHMED grade revealed that the T1ρ and the T2 measurements of the PHMED and the medial tibial (MT) cartilage were higher in subjects having a meniscal tear (meniscal grade 2–4) compared to subjects with a meniscal grade of 0 or 1 (P

SummaryObjectiveThe aim of this study was to assess the reproducibility of meniscus T1ρ measurements, and to study T1ρ relaxation time in the lateral meniscus (LM) and its relationship with adjacent cartilage T1ρ in knees with acute anterior cruciate ligament (ACL) injuries at 3T magnetic resonance imaging.MethodQuantitative assessment of the meniscus and cartilage was performed in 15 healthy controls and 16 ACL-injured patients using a T1ρ mapping technique. All ACL-injured patients were imaged prior to surgery within 1–3 months of injury. The anterior and posterior horns of LM and medial meniscus (MM) were associated with partitioned weight-bearing cartilage sub-compartments (anterior, central, and posterior).ResultsT1ρ measurements in the meniscus showed excellent reproducibility (coefficient of variation (CV)

SummaryObjectiveTo evaluate trabecular bone structure in relationship with cartilage parameters in distal femur and proximal tibia of the human knee at 3Tesla (3T) using high-resolution magnetic resonance imaging (MRI) with parallel imaging.MethodSixteen healthy controls and 16 patients with mild osteoarthritis (OA) were studied using a 3T magnetic resonance (MR) scanner and an eight-channel phased-array knee coil. Axial 3D GeneRalized Autocalibrating Partially Parallel Acquisition (GRAPPA)-based phase cycled Fast Imaging Employing Steady State Acquisition (FIESTA-c) images were acquired in order to quantify the trabecular bone structure. For assessing cartilage morphology (thickness, volume), sagittal high-resolution 3D spoiled gradient echo (SPGR) images were acquired. In a subset of the subjects, sagittal images were acquired for measuring T1ρ and T2 relaxation times, using 3D T1ρ and T2 mapping techniques.ResultsGood measurement reproducibility was observed for bone parameters, the coefficients of variations (CVs) ranging from 1.8% for trabecular number (app. Tb.N) to 5.5% for trabecular separation (app. Tb.Sp). Significant differences between control and OA groups were found for bone volume fraction bone volume over total volume (app. BV/TV) and app. Tb.Sp in all compartments. Significantly increased values in T1ρ and T2 were demonstrated in OA patients compared with controls at the femur, but not at the tibia. T1ρ was negatively correlated with app. BV/TV, app. Tb.N and app. Tb.Sp both at the medial femoral condyle (MFC) and lateral tibia (LT), while T2 was only correlated at the LT. Also, medial tibia (MT) T1ρ was negatively correlated with app. BV/TV (R2=−0.49, P

To assess the reproducibility of quantitative measurements of cartilage morphology and trabecular bone structure of the knee at 7 T, high-resolution sagittal spoiled gradient-echo images and high-resolution axial fully refocused steady-state free-precession (SSFP) images from six healthy volunteers were acquired with a 7-T scanner. The subjects were repositioned between repeated scans to test the reproducibility of the measurements. The reproducibility of each measurement was evaluated using the coefficient(s) of variation (CV). The computed CV were 1.13% and 1.55% for cartilage thickness and cartilage volume, respectively, and were 2.86%, 1.07%, 2.27% and 3.30% for apparent bone volume over total volume fraction (app.BV/TV), apparent trabecular number (app.Tb.N), apparent trabecular separation (app.Tb.Sp) and apparent trabecular thickness (app.Tb.Th), respectively. The results demonstrate that quantitative assessment of cartilage morphology and trabecular bone structure is reproducible at 7 T and motivates future musculoskeletal applications seeking the high-field strength's superior signal-to-noise ratio.

The in vivo precision (reproducibility) of quantitative MRI is of particular importance in osteoarthritis (OA) progression of small magnitude and response to therapy. In this study, three-dimensional high-resolution MRI performed at 7 T was used to assess the short-term reproducibility of measurements of mean tibial cartilage thickness in a meniscectomized guinea pig model of OA. MR image acquisition was repeated five times in nine controls (SHAM) and 10 osteoarthritic animals 3 months after meniscectomy (MNX), in vivo. The animals were then killed for histomorphometric assessment and correlation with the MRI-based measurements. Medial tibial cartilage thickness was measured on MR images using semi-automatic dedicated 3D software developed in-house. The reproducibility of measurements of cartilage thickness was assessed by five repeated MRI examinations with a short recovery delay between examinations (48 h). The computed coefficients of variation were 8.9% for the SHAM group and 8.2% for the MNX group. The coefficients of variation were compatible with expected thickness variations between normal and pathological animals. A positive agreement and significant partial correlation (Spearman r′ = 0.74; P

SummaryObjectiveThe aim of this study was to follow, over a 4½-month period, the medial tibia cartilage thickness on a meniscectomy (MNX) guinea pig osteoarthritis (OA) model and to compare with control animals, using three-dimensional high-resolution magnetic resonance imaging (3D HR-MRI).MethodsMRI experimentations were performed in vivo at 7T on guinea pig knee joints. 3D HR-MR images were acquired in 60 controls (SHAM) and 45 osteoarthritic animals (MNX) at four time-points (15, 45, 90 and 135 days) after surgery. Medial tibial cartilage thickness was measured from MRI images using in-house dedicated 3D software followed by a statistical analysis. At each time-point 15 SHAM and 15 MNX animals were sacrificed for histomorphometric assessments.ResultsNo significant difference of mean cartilage thickness between the groups was found at early stage (D45) using MRI; however, significant differences were found between the groups at D90 (P

Background Glioblastoma (GBM) is the most frequent and aggressive type of adult brain tumor. Most GBMs express telomerase; a high level of intra-tumoral telomerase activity (TA) is predictive of poor prognosis. Thus, telomerase inhibitors are promising options to treat GBM. These inhibitors increase the response to radiotherapy (RT), in vitro as well as in vivo. Since typical treatments for GBM include RT, our objective was to evaluate the efficiency of Imetelstat (TA inhibitor) combined with RT. Findings We used a murine orthotopic model of human GBM (N = 8 to11 mice per group) and μMRI imaging to evaluate the efficacy of Imetelstat (delivered by intra-peritoneal injection) alone and combined with RT. Using a clinically established protocol, we demonstrated that Imetelstat significantly: (i) inhibited the TA in the very center of the tumor, (ii) reduced tumor volume as a proportion of TA inhibition, and (iii) increased the response to RT, in terms of tumor volume regression and survival increase. Conclusions Imetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0376-3) contains supplementary material, which is available to authorized users.

The application of biomolecular magnetic resonance imaging becomes increasingly important in the context of early cartilage changes in degenerative and inflammatory joint disease before gross morphological changes become apparent. In this limited technical report, we investigate the correlation of MRI T1, T2 and T1 relaxation times with quantitative biochemical measurements of proteoglycan and collagen contents of cartilage in close synopsis with histologic morphology. A recently developed MR imaging sequence, T1, was able to detect early intracartilaginous degeneration quantitatively and also qualitatively by color mapping demonstrating a higher sensitivity than standard T2-w sequences. The results correlated highly with reduced proteoglycan content and disrupted collagen architecture as measured by biochemistry and histology. The findings lend support to a clinical implementation that allows rapid visual capturing of pathology on a local, millimeter level. Further information about articular cartilage quality otherwise not detectable in-vivo, via normal inspection, is needed for orthopedic treatment decisions in the present and future.

Objective To assess OA-related changes in mean compartmental femorotibial cartilage thickness in rat knees by three-dimensional (3D) MRI (7T). Methods MRI was performed in vivo at 7T on OA and untouched contralateral knee joints. Gradient Echo Fast Imaging 3D MR images were acquired sequentially in surgically induced OA (D0) in 40 Wistar rats (anterior cruciate ligament transection). Mean femoral (trochlear, lateral and medial) and tibial (lateral and medial) cartilage thicknesses were quantified from a 2D MRI slide in weight-bearing areas and from a 3D MRI data set. At each time-point [Day (D)8, D14, D21, D40 and D60], eight animals (16 knees) were sacrificed for concomitant histomorphometry. Results As body weight dramatically increased throughout the experiment (+150%, baseline vs endpoint), all compartmental mean cartilage thicknesses noticeably decreased (D8, D14) and then remained relatively stable. Femoral compartments in OA knees were thinner at the end of the experiment than in contralateral age-matched knees. Conversely, lateral and medial tibial cartilages were thicker than controls. Histological correlation was significant only in untouched healthy cartilages (3D better than 2D). Conclusions 3D MRI (7T) enables in vivo monitoring of compartmental changes in OA-related femorotibial rat cartilage thickness vs contralateral age-matched knees.

Purpose A direct correlation between T1ρ, T2 and quantified proteoglycan and collagen contents in human osteoarthritic cartilage has yet to be documented. We aimed to investigate the orientation effect on T1ρ and T2 values in human osteoarthritic cartilage and to quantify the correlation between T1ρ, T2 vs. biochemical composition and histology in human osteoarthritic cartilage. Materials and methods Thirty-three cartilage specimens were collected from patients who underwent total knee arthroplasty due to severe osteoarthritis and scanned with a 3T MR scanner for T1ρ and T2 quantification. Nine specimens were scanned at three different orientations with respect to the B0: 0°, 90° and 54.7°. Core punches were taken after MRI. Collagen and proteoglycan contents were quantified using biochemical assays. Histology sections were graded using Mankin scores. The correlation between imaging parameters, biochemical contents and histological scores were studied. Results Both mean T1ρ and T2 at 54.7° were significantly higher than those measured at 90° and 0°, with T1ρ showing less increase compared to T2. R1ρ (1/T1ρ) values had a significant but moderate correlation with proteoglycan contents (R=.45, P=.002), while R2 (1/T2) was not correlated with proteoglycan. No significant correlation was found between relaxation times (T1ρ or T2) and collagen contents. The T1ρ values of specimen sections with high Mankin scores were significantly higher than those with low Mankin scores (P Conclusions Quantitative MRI has a great potential to provide noninvasive imaging biomarkers for cartilage degeneration in osteoarthritis.

International audience; In the field of small animal studies, the array coil imaging has become increasingly important. In this paper, a dedicated two-channel array coil operating at 300 MHz (7 T) for high-resolution MRI (HR-MRI) of the rat knee cartilage is presented. The average gain in signal-to-noise ratio (SNR) compared to a 15-mm multipurpose surface coil was 2.2. This SNR gain was used to improve the spatial resolution of 3-D acquisitions by decreasing the voxel size from 59 x 59 x 156 microm(3) to 51 x 51 x 94 microm(3) without time penalty. Also, a set of two array coils was used to perform a simultaneous acquisition of both knee joints of a rat, maintaining the same scanning time without SNR or spatial resolution degradation compared to the single knee joint acquisition. This two-channel array coil is a key element to perform HR-MRI and extract cartilage morphological parameters such as thickness and volume.

To quantitate bone marrow edema-like lesions (BMELs) and the radiologic properties of cartilage in knees with acute anterior cruciate ligament (ACL) injuries using T(1ρ) magnetic resonance imaging over a 1-year period.Nine patients with ACL injuries were studied. Magnetic resonance imaging scans were acquired within 8 weeks of the injury, after which ACL reconstruction surgery was performed. Images were then acquired 0.5, 6, and 12 months after reconstructions. The volume and signal intensity of BMELs were quantified at baseline and follow-up examinations. T(1ρ) values were quantified in cartilage overlying the BMEL (OC) and compared with surrounding cartilage at all time points.BMELs were most commonly found in the lateral tibia and lateral femoral condyle. Nearly 50% of BMELs resolved over a 1-year period. The T(1ρ) values of the OC in the lateral tibia, medial tibia, and medial femoral condyle were elevated compared with respective regions in surrounding cartilage at all time points; the difference was significant only in the lateral tibia (P.05). The opposite results were found in the lateral femoral condyle. For the medial tibia and medial femoral condyle, none of the time periods was significantly different. The percent increase in T(1ρ) values of OC in the lateral tibia was significantly correlated with BMEL volume (r = 0.74, P.05). At 1 year, the OC in the lateral tibia, medial tibia, and medial femoral condyle showed increased T(1ρ) values despite improvement of BMEL.In patients after ACL tear and reconstruction, (1) the cartilage overlying BMEL in the lateral tibia experiences persistent T(1ρ) signal changes immediately after acute injuries and at 1-year follow-up despite BMEL improvement, (2) the superficial layers of the overlying cartilage show greater matrix damage than the deep layers, and (3) the volume of the BMEL may predict the severity of the overlying matrix's damage in the lateral tibia. T(1ρ) is capable of quantitatively and noninvasively monitoring this damage and detecting early cartilage changes in the lateral tibia over time.Level IV, therapeutic case series.

To quantitatively assess the relationship between bone marrow edema-like lesions (BMELs) and the associated cartilage in knee osteoarthritis (OA) using T(1rho) quantification at 3 T MRI.Twenty-four patients with knee OA and 14 control subjects underwent 3 T MRI. Nineteen patients and all control subjects had 1-year follow-up studies. The volume and signal intensity difference of BMELs were calculated. Cartilage degeneration was graded using the cartilage subscore of Whole-Organ MRI Score (WORMS) analysis. Cartilage T(1rho) values were calculated in each compartment as well as in cartilage overlying BMELs (OC) and surrounding cartilage (SC).At baseline, 25 BMELs were found in 16 out of 24 patients. The overall T(1rho) values were significantly higher in patients with BMELs than in those without BMELs. At baseline and follow-up, both T(1rho) values and WORMS cartilage subscore grading were significantly higher in OC than SC. Cartilage T(1rho) increase from baseline to follow-up in OC was significantly higher than that in SC. An increase in T(1rho) values in OC was correlated with signal intensity of BMEL at both baseline and follow-up, but was not correlated with BMEL volume.The results of this study suggest a local spatial correlation between BMELs and more advanced and accelerated cartilage degeneration. MRI T(1rho) quantification in cartilage provides a sensitive tool for evaluating such correlations.

The anterior cruciate ligament (ACL) is the most commonly torn ligament in the knee, with more than 80,000 injuries occurring annually in the United States alone.1 The rupture of the ACL frequently occurs in young active individuals. The injury is usually a result of a valgus and internal rotational torque to the knee. During the injury, the knee can sublux after ACL rupture and the lateral femoral condyle (LFC) can impact the posterior aspect of the lateral tibia, resulting in the classic bone marrow edema-like lesions (BMELs) or osteochondral lesions within the lateral compartment, also known as the “kissing lesions.”2 The prevalence of BMEL in patients with ACL injuries has been reported to be up to 70% to 80%.3,4 The BMEL is usually located in the middle portion of the lateral femoral condyle and the posterior portion of the lateral tibial plateau. Despite the high prevalence of these BMEL with ACL ruptures, little is known about the clinical consequences of these findings or about their relationship with local and global cartilage degeneration. Magnetic resonance imaging (MRI) is a useful diagnostic tool for ACL tears and related injuries.5 BMEL detected with MRI has been described previously as focally signal hyperintensity in the bone marrow on fat-suppressed T2-weighted MR images or in short inversion time inversion-recovery images due to multiple factors such as abnormal trabeculae, bone marrow necrosis, marrow hemorrhage, and marrow edema.6 The formation of bone bruises has been shown to cause substantial damage to the articular cartilage leading to cell death of a significant number of chondrocytes.7 Despite ACL reconstruction to correct instability, a significant proportion of patients develop clinical symptoms of osteoarthritis (OA) 5 to 10 years postinjury.8,9 These findings suggest that initial injury to the articular cartilage may predispose the joint to the development of OA. Therefore, a detailed topographic analysis of the articular cartilage is important to identify local cartilage degeneration after ACL injury. Quantitative MRI is a noninvasive technique for assessing acute knee injuries and can play an important role in determining treatment options and evaluating surgical interventions. In cartilage, the proteoglycan (PG) is largely responsible for the high elasticity and resilience of tissue. The PG content of cartilage can be probed using spin lattice relaxation in the rotating frame: T1ρ-weighted imaging.10 This particular quantitative method based on spin-locking technique reflects the slow motion interactions between motion-restricted water molecules and their local macromolecular environment. T1ρ mapping has recently been proposed as a potential of MRI to reflect changes in the biochemical composition of cartilage with early OA, such as PG loss.11–13 Several recent ex vivo14 and in vivo15 studies investigated this relaxation technique in human OA, suggesting that T1ρ relaxation time increases with the degree of OA. Our previous case report on quantitative MRI has demonstrated that cartilage injury was present overlying BMEL after ACL injuries.16 In that report, elevated T1ρ relaxation time was found over the lateral tibia confirmed with arthroscopic findings of cartilage injury. This study prompted our current clinical evaluation on determining the severity of cartilage injury over BMEL. The goal of this study was to assess cartilage overlying areas of BMEL versus surrounding cartilage and to analyze defined cartilage compartments using T1ρ quantification in patients with acute ACL tears. The hypothesis of the study is that the cartilage degeneration can occur during acute ACL injuries. We also hypothesized that there can be a different T1ρ quantification at various regions of the knee. In this study, we compared T1ρ quantification in patients with acute ACL injuries versus healthy individuals.

BONE MARROW EDEMA PATTERN is defined as an area of high signal intensity in T2-weighted, fat-saturated magnetic resonance (MR) images or in short inversion time inversion-recovery (STIR) images. These lesions are present in knee osteoarthritis (OA) (1-3) and acute knee injuries, frequently associated with anterior cruciate ligament (ACL) tear (4-6). Although termed as “edema,” these lesions have shown surprisingly little edema based on histopathologic examination (7). Instead, this increase in signal has been attributed to a number of other factors, including abnormal trabeculae, bone marrow necrosis, swelling of fat cells, and marrow bleeding. Therefore, in this study, we term these lesions as bone marrow edema-like lesion (BMEL). While MR findings of BMEL are common, our knowledge concerning their natural history and significance is limited. In ACL tears, BMEL indicates a so-called bone bruise or impression fracture due to translational injury, where the anterolateral femur impacts the posterolateral tibia (kissing contusions) when the ACL is ruptured. A number of studies have proposed that the overlying cartilage has sustained irreversible injury during impact, and thus, cartilage degeneration can continue to occur despite the fact that functional stability of the knee is restored following ACL reconstruction (8,9). In OA, BMEL has been associated with the severity and progression of OA (2,10), and pain in OA (10,11). However, the causal relationship between these lesions and the disease progression is unclear. Better understanding of the interrelation of cartilage and the bone immediately under it is also necessary. Recent advances in MRI allow quantitative measures of volumetric and biochemical changes of cartilage prior to macroadaptive changes seen on traditional radiographs. In particular, T1ρ has been proposed as an attractive candidate to probe the early changes in cartilage extracellular matrix (ECM) during early stages of cartilage degeneration (12-15). T1ρ describes the spin-lattice relaxation in the rotating frame. It provides low-frequency information and probes changes in macromolecules. T1ρ relaxation rate (1/T1ρ) has been shown to decrease linearly with decreasing proteoglycan (PG) content in ex vivo bovine patellae (16). In vivo studies have also shown increased cartilage T1ρ values for patients with OA (17-19). One difficulty in studying BMEL lies in quantification of these lesions due to its ill-defined shape in MR images. Most previous imaging studies used qualitative (presence of high signal or not) (4,6,11), or semiquantitative evaluations (scoring the size of bone bruise volume) (1,10). Recent studies on measuring volume of BMEL manually or semiautomatically using MR images provide potential for quantitative evaluation of such lesions (5,20-22). Such quantification of BMEL may allow better classification of these lesions and potentially a better prediction to their prognosis. Furthermore, proton MR spectroscopy (MRS) provides a noninvasive method for quantifying biochemical or metabolic changes in tissues. 3D MR spectroscopic imaging (MRSI) will further allow examining the spatial distribution of the metabolic levels. In the case of bone marrow, the water and lipids contents are of interest (23-26). Different compartments of lipids can be also investigated using MRS. Of particular interest are indices that provide measures of the unsaturation levels among the triglycerides, which may have potential medical applications (27,28). MRS has been used widely in cerebral imaging and other tissues/organs such as prostate, breast, and muscle. However, few studies have investigated MRS in knee bone marrow (29). The objective of this study was to apply quantitative MRI and 3D MRSI methods to assess BMEL in patients with OA and ACL tears. Specifically, the goals were: 1) to establish an automatic method to calculate the volume of BMEL; 2) to quantify water and lipids changes in BMEL using 3D MRSI; and 3) to assess composition changes in cartilage overlying areas of BMEL using measurements of T1ρ relaxation time.

OBJECTIVES to assess reliability and reproducibility of quantitative MRI (7 T) in assessing rat femoro-tibial cartilage volume. METHODS 5 healthy rat knees were scanned in vivo using a 7 T experimental imager. Sagittal high resolution 3D Gradient Echo with fat suppression sequences were performed with a dedicated home-made 2-elements array coil. 3D MRI sets were used to perform manual segmentation of the 3 cartilage compartments (femoral groove, medial and lateral tibial plateaus) by using a tactile screen. To evaluate inter- and intra-observer reproducibilities, the segmentation procedure was done blindly by two trained observers. One observer repeated the operation twice, with a period of 10 months between both readings. RESULTS the mean duration to manually segment all the slices covering the cartilaginous joint was 4 hours. On the one hand, the inter-observer root mean square of coefficients of variation was 9.1%, 6.2%, 9.6% for the femoral, medial and lateral tibial compartments respectively. On the other hand, the intra-observer reproducibility was 2.1%, 3.2%, 2.5% for these cartilage compartments cited above. CONCLUSION the image quality obtained at 7 Teslas with our dedicated coil allowed segmentation of the cartilage compartments with good reproducibility. This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of rat knee cartilage volume.

We present an adaptive solution for guinea pig knee cartilage segmentation using a 3-D smoothing B-Spline active surface. An adaptive parametric combination of edge-based forces and balloon force solves the problem of capture range of external forces. The comparison between the results of the experiments using this method and previous 3-D validated snake segmentation shows that the accuracy and robustness are improved.

Despite that on clinical systems phased array technology is now widely used, the high field MRI experimental systems with multiple receiver channels just became available few years ago. For this reason and due to the large range of magnetic field (frequencies between 200 and 500 MHz for proton resonance), commercial phased arrays implemented in narrow bore for high field applications are rare and relatively expensive. Array coil imaging is an advanced method for acquiring high resolution images with enhanced signal-to-noise ratio (SNR) and/or enlarged field of view (FOV) compared for example to single loop surface coil. The volume of interest is then covered by several coil elements and images reconstructed for every single channel are combined afterwards. The goal of this work was to develop a dedicated two-element array coil operating at 300 MHz (7 T) for high-resolution imaging of rat knee joint in order to quantify cartilage thickness and volume. A dedicated two-element array coil with two square elements encompassing knee joint was designed and built. Decoupling between elements was achieved with a capacitor inserted on the common leg of the two elements. The average gain in SNR compared to a 15 mm reference single loop coil was 2.2. This SNR gain was used to improve spatial resolution of 3D acquisition by decreasing the voxel size from 59 x 59 x 156 mum3 to 51 x 51 times 94 mum3 without time penalty. This two element array coil is a key element to perform HR-MRI and extract morphological parameters of animal cartilage. Finally, a set of two array coils were used to perform the acquisition of both rat knee joint at the same time with no additional acquisition time or resolution decrease.

Keywords: Mri ; cartilage ; articular contact ; morphology ; rat ; Articular-Cartilage Reference EPFL-CONF-169141doi:10.1080/10255840802298786View record in Web of Science Record created on 2011-09-29, modified on 2017-05-12

Introduction L’IRM champs eleves 3 dimensions (3D) a haute resolution (HR) permettant d’optimiser la qualite des images est un outil de recherche interessant pour etudier le cartilage articulaire des petites articulations de facon non-invasive. A partir des donnees 3D de l’IRM, nous avons realise des mesures quantitatives de volumes et d’epaisseurs du cartilage qui furent confrontees aux donnees histologiques classiques. Materiel et Methodes 48 rats Wistar mâles ont subi une section du ligament croise anterieur du genou droit selon un protocole standardise, le genou gauche servant de temoin. Les genoux etaient explores par IRM in vivo a 7T (sequence 3D echo de gradient, suppression du signal de la graisse, antenne specifique a deux elements en reseau) a J7, J14, J28, J42 et J56. Apres l’acquisition, les animaux etaient sacrifies pour l’etude histologique. Des coupes histologiques sagittales colorees par l’hematoxyline-eosine-safran etaient realisees, correspondant aux zones articulaires portantes selectionnees en IRM. Pour les deux techniques d’imagerie, les cartilages femoraux et tibiaux etaient segmentes manuellement. Les masques binaires resultants permettaient de determiner les volumes et epaisseurs (confrontations IRM-histologie) du cartilage articulaire. Resultats Concernant l’epaisseur du cartilage, il existait une correlation significative p = 0,02 entre l’IRM et l’histologie, au niveau femoral et tibial. Les valeurs des scores histologiques (membrane synoviale et cartilage) sont significativement differentes entre les genoux operes et temoins. Le suivi de la progression arthrosique en IRM montre d’importantes lesions degeneratives avec pertes cartilagineuses predominant au niveau du compartiment femoral, le compartiment tibial etant plutot le siege de phenomenes inflammatoires et oedemateux. Une correlation significative existait entre les mesures d’epaisseur relevees en IRM et en histologie (femur : r = 0,45 ; p = 0,02 ; tibia : r = 0,47 ; p = 0,01). Conclusion L’IRM 3D HR a 7T permet l’analyse in vivo de la progression arthrosique chez le rat. Les valeurs quantitatives obtenues en IRM sont compatibles avec les variations d’epaisseurs relevees en histologie. Une correlation significative est etablie entre ces deux techniques. L’IRM 3D HR a 7T est un outil non-invasif prometteur pour l’evaluation et le suivi in vivo de reponses therapeutiques chez le rongeur arthrosique.