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Ultrashort echo-time imaging and sweep imaging with Fourier transformation are powerful techniques developed for imaging ultrashort T(2) species. However, it can be challenging to implement them on standard clinical MRI systems due to demanding hardware requirements. In this article, the limits of what is possible in terms of the minimum echo-time and repetition time with 3D radial gradient-echo sequences, which can be readily implemented on a standard clinical scanner, are investigated. Additionally, a new 3D radial gradient-echo sequence is introduced, called COncurrent Dephasing and Excitation (CODE). The unique feature of CODE is that the initial dephasing of the readout gradient is performed during RF excitation, which allows CODE to effectively achieve echo-times on the order of ∼0.2 ms and larger in a clinical setting. The minimum echo-time achievable with CODE is analytically described and compared with a standard 3D radial gradient-echo sequence. CODE was implemented on a clinical 3 T scanner (Siemens 3 T MAGNETOM Trio), and both phantom and in vivo human knee images are shown for demonstration.

A new method entitled Relaxation Along a Fictitious Field (RAFF) was recently introduced for investigating relaxations in rotating frames of rank ⩾2. RAFF generates a fictitious field (E) by applying frequency-swept pulses with sine and cosine amplitude and frequency modulation operating in a sub-adiabatic regime. In the present work, MRI contrast is created by varying the orientation of E, i.e. the angle e between E and the z″ axis of the second rotating frame. When e > 45°, the amplitude of the fictitious field E generated during RAFF is significantly larger than the RF field amplitude used for transmitting the sine/cosine pulses. Relaxation during RAFF was investigated using an invariant-trajectory approach and the Bloch–McConnell formalism. Dipole–dipole interactions between identical (like) spins and anisochronous exchange (e.g., exchange between spins with different chemical shifts) in the fast exchange regime were considered. Experimental verifications were performed in vivo in human and mouse brain. Theoretical and experimental results demonstrated that changes in e induced a dispersion of the relaxation rate constants. The fastest relaxation was achieved at e ≈ 56°, where the averaged contributions from transverse components during the pulse are maximal and the contribution from longitudinal components are minimal. RAFF relaxation dispersion was compared with the relaxation dispersion achieved with off-resonance spin lock T1ρ experiments. As compared with the off-resonance spin lock T1ρ method, a slower rotating frame relaxation rate was observed with RAFF, which under certain experimental conditions is desirable.

Articular cartilage assessment in femoroacetabular impingement (FAI) is challenging. Recent studies on T2* relaxation time mapping suggest the technique may be useful in diagnosing cartilage damage. The purpose of this case report is to describe how quantitative T2*-mapping may improve cartilage assessment of the acetabulum in patients with FAI. MR arthrography was performed at 3 Tesla (T) using intra-articular Gadolinium and a T2* mapping protocol. Data from the acetabular cartilage was separated from femoral head cartilage data and then superimposed on a flattened, map projection representation of the patient's acetabulum. The areas of unhealthy cartilage observed at the time of arthroscopy – including debonding and delamination – were seen preoperatively at the same anatomic locations as areas of decreased T2* values. T2* mapping values provided a non-invasive assessment of the acetabular articular cartilage. A flattened acetabular map projection allowed for anatomic visualization of areas of unhealthy cartilage. Level of evidence Level IV.

Background There has recently been increased interest in the use of 7.0-T magnetic resonance imaging for evaluating articular cartilage degeneration and quantifying the progression of osteoarthritis. Purpose The purpose of this study was to evaluate articular cartilage cross-sectional area and maximum thickness in the medial compartment of intact and destabilized canine knees using 7.0-T magnetic resonance images and compare these results with those obtained from the corresponding histologic sections. Study Design Controlled laboratory study. Methods Five canines had a surgically created unilateral grade III posterolateral knee injury that was followed for 6 months before euthanasia. The opposite, noninjured knee was used as a control. At necropsy, 3-dimensional gradient echo images of the medial tibial plateau of both knees were obtained using a 7.0-T magnetic resonance imaging scanner. Articular cartilage area and maximum thickness in this site were digitally measured on the magnetic resonance images. The proximal tibias were processed for routine histologic analysis with hematoxylin and eosin staining. Articular cartilage area and maximum thickness were measured in histologic sections corresponding to the sites of the magnetic resonance slices. Results The magnetic resonance imaging results revealed an increase in articular cartilage area and maximum thickness in surgical knees compared with control knees in all specimens; these changes were significant for both parameters (P 1). Conclusion These results demonstrate that 7.0-T magnetic resonance imaging provides an alternative method to histology to evaluate early osteoarthritic changes in articular cartilage in a canine model by detecting increases in articular cartilage area. Clinical Relevance The noninvasive nature of 7.0-T magnetic resonance imaging will allow for in vivo monitoring of osteoarthritis progression and intervention in animal models and humans for osteoarthritis.

In vivo visualization of subclinical osteochondrosis(OC) lesions, characterized by necrosis of epiphyseal growth cartilage, is necessary to clarify the pathogenesis of this disease. Hence, our objectives were to demonstrate induced necrosis of the epiphyseal cartilage in vivo using MRI and to monitor progression or resolution of resulting lesions. We also aimed to improve the goat model of OC by introducing controlled exercise. Vascular supply to the epiphyseal cartilage was surgically interrupted in four 5-day-old goats to induce ischemic cartilage necrosis in a medial femoral condyle. Starting 3 weeks postoperatively, goats underwent daily controlled exercise until euthanasia at 6, 10, 11 (n=2) weeks postoperatively. T2 maps of operated and control femora were obtained in vivo at 3(n=4), 6(n=4), 9(n=3) and 11(n=2) weeks postoperatively using a 3T MR scanner. In vivo MRI findings were validated against MRI results obtained ex vivo at 9.4T in three goats and compared to histological results in all goats. Surgical interruption of the vascular supply caused ischemic cartilage necrosis in 3 out of 4 goats. T2 maps obtained in vivo at 3T identified regions of increased relaxation time consistent with discrete areas of cartilage necrosis 3 to 11 weeks postoperatively and demonstrated delayed progression of the ossification front at 9(n=1) and 11(n=2) weeks postoperatively. In vivo MRI findings were confirmed by ex vivo MRI at 9.4T and by histology. Identification of cartilage necrosis in clinical patients in the early stages of OC using T2 maps may provide valuable insight into the pathogenesis of this condition.

Image blurring that results from off-resonance and fast T2* signal decay is a common issue in radial ultrashort echo time magnetic resonance imaging (MRI) sequences. One solution is to use a higher readout bandwidth, but this may be impractical for some techniques such as pointwise-encoding time reduction with radial acquisition (PETRA), which is a hybrid method of zero echo time and single-point imaging techniques. Specifically, PETRA has severe specific absorption rate (SAR) and radiofrequency (RF) pulse peak power limitations when using higher bandwidths in human measurements. In this study, we introduce gradient modulation (GM) to PETRA to reduce image-blurring artifacts while keeping SAR and RF peak power low. GM-PETRA tolerance to image blurring was evaluated in simulations and experiments by comparison with the conventional PETRA technique. We performed inner ear imaging of a healthy subject at 7 T. GM-PETRA showed significantly less image blurring as a result of off-resonance and fast T2* signal decay compared to PETRA. In in vivo imaging, GM-PETRA nicely captured complex structures of the inner ear such as the cochlea and semicircular canals. GM can improve PETRA image quality and mitigate SAR and RF peak power limitations without special hardware modification in clinical scanners.

Background: Understanding the pathogenesis of osteochondrosis/osteochondritis dissecans and other developmental orthopaedic diseases that are thought to occur secondary to defects in vascular supply to growth/epiphyseal cartilage has been hampered by the inability to image the vasculature in this tissue. This is particularly true in human beings due to limitations of current imaging techniques and the lack of availability of appropriate cadaveric samples for histological studies. Hypothesis: Susceptibility-weighted imaging, an MRI sequence, allows identification of characteristic differences in the vascular architecture in species that are affected by osteochondrosis/osteochondritis dissecans on the femoral condyle (humans and pigs) versus a species that is free of the disease (goat). Study Design: Controlled laboratory study. Materials: Distal femora from cadavers of juvenile humans (n = 5), pigs (n = 3), and goats (n = 3) were scanned in a 9.4-T MRI scanner using susceptibility-weighted imaging. Three-dimensional reconstructions were created, and minimum intensity projections were calculated in 3 planes to enhance visualization of the vascular architecture. Results: Susceptibility-weighted imaging allowed clear visualization of the epiphyseal vasculature in all species. Vascular architecture, with vessels primarily arising from the perichondrium, was similar in humans and pigs, which are predisposed to osteochondrosis/osteochondritis dissecans, and was starkly different from that present in goats, a species in which there are no reports of osteochondrosis/osteochondritis dissecans. Furthermore, vessels in the distal femoral predilection site disappeared with age in humans in a pattern similar to that reported previously in pigs. Conclusion: Nearly identical vascular architecture at the shared primary predilection site of osteochondrosis/osteochondritis dissecans in the femoral condyles in human beings and pigs suggests that vascular failure, which is known to be central to the pathogenesis of this disease in pigs, may also play a role in humans. Clinical Relevance: This assumption of a shared pathogenesis is supported by the pattern of disappearance of vessels with age at the primary predilection site of osteochondritis dissecans in humans, which is essentially identical to that which has been reported in pigs. Susceptibility-weighted imaging will likely help further elucidate this potential relationship in the future.

Article, Purpose Cartilage canal vessels are critical to the normal function of epiphyseal (growth) cartilage and damage to these vessels is demonstrated or suspected in several important developmental orthopaedic diseases. High-resolution, three-dimensional (3-D) visualization of cartilage canals has recently been demonstrated using susceptibility weighted imaging (SWI). In the present study, a quantitative susceptibility mapping (QSM) approach is evaluated for 3-D visualization of the cartilage canals. It is hypothesized that QSM post-processing improves visualization of the cartilage canals by resolving artifacts present in the standard SWI post-processing while retaining sensitivity to the cartilage canals. Methods Ex vivo distal femoral specimens from 3- and 8-week-old piglets and a 1-month-old human cadaver were scanned at 9.4 T with a 3-D gradient recalled echo sequence suitable for SWI and QSM post-processing. The human specimen and the stifle joint of a live, 3-week-old piglet also were scanned at 7.0 T. Datasets were processed using the standard SWI method and truncated k-space division QSM approach. To compare the post-processing methods, minimum/maximum intensity projections and 3-D reconstructions of the processed datasets were generated and evaluated. Results Cartilage canals were successfully visualized using both SWI and QSM approaches. The artifactual splitting of the cartilage canals that occurs due to the dipolar phase, which was present in the SWI post-processed data, was eliminated by the QSM approach. Thus, orientation-independent visualization and better localization of the cartilage canals was achieved with the QSM approach. Combination of GRE with a mask based on QSM data further improved visualization. Conclusions Improved and artifact-free 3-D visualization of the cartilage canals was demonstrated by QSM processing of the data, especially by utilizing susceptibility data as an enhancing mask. Utilizing tissue-inherent contrast, this method allows noninvasive assessment of the vasculature in the epiphyseal cartilage in the developing skeleton and potentially increases the opportunity to diagnose disease of this tissue in the preclinical stages, when treatment likely will have increased efficacy., published version, http://purl.org/eprint/status/PeerReviewed

Article, Purpose To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC) in goats. Methods Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections. Results All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG) loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues. Conclusions Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions., published version, http://purl.org/eprint/status/PeerReviewed

Summary Objective Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. Design Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. Results Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. Conclusions Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC.

To evaluate the feasibility of SWIFT with variable flip angle (VFA) for measurement of TThe different TFeasibility of measuring T

Study Design. Experimental correlation study design to quantify features of disc health, including signal intensity and distinction between the annulus fibrosus and nucleus pulposus, with T2* magnetic resonance imaging (MRI) and correlate with the functional mechanics in corresponding motion segments. Objective. Establish the relationship between disc health assessed by quantitative T2* MRI and functional lumbar mechanics. Summary of Background Data. Degeneration leads to altered biochemistry in the disc, affecting the mechanical competence. Clinical routine MRI sequences are not adequate in detecting early changes in degeneration and fails to correlate with pain or improve patient stratification. Quantitative T2* relaxation time mapping probes biochemical features and may offer more sensitivity in assessing disc degeneration. Methods. Cadaveric lumbar spines were imaged using quantitative T2* mapping, as well as conventional T2-weighted MRI sequences. Discs were graded by the Pfirrmann scale, and features of disc health, including signal intensity (T2* intensity area) and distinction between the annulus fibrosus and nucleus pulposus (transition zone slope), were quantified by T2*. Each motion segment was subjected to pure moment bending to determine range of motion (ROM), neutral zone (NZ), and bending stiffness. Results. T2* intensity area and transition zone slope were significantly correlated with flexion ROM (P = 0.015; P = 0.002), ratio of NZ/ROM (P = 0.010; P = 0.028), and stiffness (P = 0.044; P = 0.026), as well as lateral bending NZ/ROM (P = 0.005; P = 0.010) and stiffness (P = 0.022; P = 0.029). T2* intensity area was also correlated with lateral bending ROM (P = 0.023). Pfirrmann grade was only correlated with lateral bending NZ/ROM (P = 0.001) and stiffness (P = 0.007). Conclusion. T2* mapping is a sensitive quantitative method capable of detecting changes associated with disc degeneration. Features of disc health quantified with T2* predicted altered functional mechanics of the lumbar spine better than traditional Pfirrmann grading. This new methodology and analysis technique may enhance the assessment of degeneration and enable greater patient stratification for therapeutic strategies. Conclusion. Level of Evidence: N/A

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Sweep imaging with Fourier transformation, SWIFT, is a relatively new addition to the class of ultra-short T2-sensitive MRI sequences. It reverses the recent paradigm of pulsed NMR methodology by exploiting features of continuous-wave experiments from the early days of NMR. Images are produced by collecting projections of the object in a radial manner. Each projection is excited by a frequency sweep in the presence of a field gradient. MR signal is acquired in gaps in the frequency-swept pulse, in a time-shared manner. Signals are excited sequentially in time and space, leading to phase variation. Phase variation due to the frequency-swept excitation is removed by correlation of the received data with the pulse waveform. The result is equivalent to FID excitation using a short hard pulse. The phase evolution time of signal prior to acquisition is as low as a few microseconds for high bandwidth SWIFT, so signals from spins with extremely short T2s (tens of microseconds) are preserved. Here we describe the SWIFT sequence and signal processing procedures, along with some applications, including magnetization-prepared imaging of the human brain, in vitro imaging of bone and cartilage, in vitro dental imaging, and high-resolution phase imaging of in vitro rat brain. Keywords: NMR; MRI; frequency modulation; frequency sweep; adiabatic pulses; musculoskeletal imaging; radial MRI

The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180 degrees inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T1-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI.

1. We used conventional gradient echo magnetic resonance imaging (MRI) at high field strength (4 Tesla) to functionally image the right motor cortex in six normal human subjects during the performance of a sequence of self-paced thumb to digit oppositions with the left hand (contralateral task), the right hand (ipsilateral task), and both hands (bilateral task). 2. A localized increase in activity in the lateral motor cortex was observed in all subjects during the task. The area of activation was similar in the contralateral and bilateral tasks but 20 times smaller in the ipsilateral task. The intensity of activation was 2.3 times greater in the contralateral than the ipsilateral task.

The purpose of our study was to determine if sectioning the canine fibular collateral ligament, popliteus tendon, and popliteofibular ligament would result in residual posterolateral instability and produce measureable evidence of early-onset arthritis on ultra-high field MRI. The fibular collateral ligament, popliteus tendon, and popliteofibular ligament were surgically sectioned in six canines. Six months postoperatively, both limbs were biomechanically tested involving 3.25 Nm varus and 1.25 Nm internal and external rotation torques at 28.5° (mean full extension), 60°, and 90° of flexion. A 7.0-tesla MRI scanner acquired T 1ρ-weighted images, and relaxation time constants were calculated. Compared to the non-operative knees, varus angulation significantly increased by 2.0°, 8.0°, and 12.4° in the operative knees at full extension, 60° flexion, and 90° flexion, respectively. External rotation was significantly increased by 8.1° at full extension, 12.2° at 60°, and 8.2° at 90°. Internal rotation was significantly increased by 9.1° at full extension and 12.4° at 60°. T 1ρ MRI mapping revealed a significant increase in relaxation times in the medial compartment of the surgical knees compared to controls. This study validated that grade III surgically created posterolateral knee injuries do not heal and that the canine knee developed early-onset changes of the medial compartment, indicative of early-onset osteoarthritis, developed in the operative knees.

We have used functional magnetic resonance imaging (fMRI) to study the changes in cerebellar activation that occur during the acquisition of motor skill in human subjects presented with a new task. The standard paradigm consisted of a center-out movement in which subjects used a joystick to superimposed a cursor onto viusual targets. Two variations of this paradigm were introduced: (1) a learning paradigm, where the relationship between movement of the joystick and cursor was reversed, requiring the learning of a visuomotor transformation to optimize performance and (2) a random paradigm, where the joystick/cursor relationship was changed randomly for each trial. Activation in the cerebellum was highest during the random paradigm and during the early stages of the learning paradigm. In the early stages of learning and during the random paradigm performance was poor with a decrease in the number of completed movements, and an increase in the time and length of movements. With repeated practice at the learning paradigm performance improbed and reached the same level of proficiency as in the standard task. Commensurate with the improbement in performance was a decrease in cerebellar activation, that is, activation in the cerebellum changed in a parallel, but inverse relationship with performance. Linear regression analysis demonstarated that the inverse correlation between cerebellar activation and motor performance was significant. Repeated practice at the random paradigm did not produce improvements in performance and cerebellar activity remained high. The data support the hypothesis that the cerebellum is strongly activated when motor performance is inaccurate, consistent with a role for the cerebellum in the detection of, and correction for visuomotor errors.

Easily detectable (5%-20%) transient increases in the intensity of water proton magnetic resonance (MR) signals in human primary visual cortex were observed during visual stimulation in gradient echo images at 4-T field strength. The signal intensity increases were predominantly restricted to areas containing gray matter and were used to produce high-spatial-resolution human functional brain maps. Time dependence of the functional brain maps also was monitored during visual stimulation using images acquired every approximately 5 seconds; these images with high spatial and temporal resolution demonstrated that photic stimulation first resulted in signal increases in a large area of the visual cortex followed by a reduction in the size of the area, and that signal intensity increases in the gray matter were time dependent. Reducing the image acquisition echo times reduced the amplitude of the fractional signal change, suggesting that it is produced by a change in T2 or T2*. The amplitude, sign, and echo time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral with the idea that neural activation increases regional cerebral blood flow (rCBF) with a concomitant increase in venous blood oxygenation.

Summary Ischemia (one hour) and following reperfusion (up to one hour) of the small intestine induce biochemical changes which are indices for the formation and action of oxygen free radicals and which occur predominantly during the reperfusion period. But the villi and the epithelial cells show different patterns of damage, occurring both at the end of the ischemic period and during the reperfusion period. Although the quantitative morphological changes are increased during the reperfusion in comparison with the ischemic phase the quality of the pattern of structural damage is the same in both periods of the experiment. This pattern of the damage includes: 1. the neighbourhood of groups of villi with total ischemic-lytic dissolution of the villi, of villi with damage of the epithelial cells at the tip and at the lateral area and of normal villi; 2. the different degree of structural damage of neighbouring epithelial cells within one villus whose cells are either of regular structural or damaged at subcellular organelles including the plasma membrane or of those being necrotically destroyed and on the way of release into the luminal space; 3. a differentiation of the structural changes of the microvilli and other organelles within single and neighbouring epithelial cells. The biochemical findings on purine nucleotide metabolism and on the formation of oxygen free radicals as “mean values” of a homogenate from a large group of cells cannot reflect the morphological-ultrastructural changes of single villi or even single epithelial cells. The possible reasons for the mosaicism of the morphological changes during ischemia and reperfusion are discussed.

A man sustained a left knee injury which led to full-thickness chondral defects of the trochlear groove and lateral femoral condyle. Both areas were treated with microfractures and evaluated at 5 months and 2 years with standard MRI scans, T2 relaxation maps, and arthroscopy. At 5-months post-microfracture repair, the patient complained of recurrent anterior knee pain. While standard MRI imaging was inconclusive with regards to a potential recurrent defect at the trochlear groove microfracture area, T2 relaxation maps established the integrity of the surface layer which was confirmed by arthroscopic evaluation. At 2 years, imaging studies revealed repair tissue loss with low T2 values at the trochlear repair site. The failure of the trochlear site and the integrity of the lateral femoral condyle repair sites were confirmed by arthroscopy. This case report is the first one to provide a correlation of T2 mapping MRI findings with arthroscopic confirmation in the context of microfracture repairs. The study provides evidence for the clinical utility of T2 relaxation maps for the postoperative assessment of microfractures and raises the potential for T2 mapping MRI as a tool to evaluate these repair procedures.

Summary Repeated phases of hypoxia (8 h daily for 2 to 5 days at p O 2 11.33 kPa = 5.000 m in altitude) were induced to Sprague-Dawley rats in the postnatal period as well as up to the 64th day of age, and after different recovery phases the ultrastructure of hepatocytes was qualitatively and quantitatively analysed. Major results were as follows: 1. Increases in body and liver weights were delayed but were balanced off after 64 days. 2. Qualitative alterations are reversible spherical transformations of mitochondria, a degradation of lipids and a slight increase in autophagocytosis. 3. The quantitative mitochondrial parameters (volume density, number per unit area, average volume) were not even adjusted to control values after 64 days. Granular endoplasmic reticulum and ribosomes/polysomes were insignificantly reduced in comparison to control animals, structure and arrangement are regular. Lipids and glycogen were differently altered. 4. The findings of the hepatocytes after postnatal hypoxia were reversible, though the majority of parameters had not yet returned to normal after 2 months. An adaptation to repetitive hypoxic conditions is not provable.

s / Osteoarthritis and Cartilage 21 (2013) S63–S312 S110 inadequate barium perfusion. Future studies of cartilage canals using SWI are likely to improve our understanding of the pathogenesis and progression of OC and other developmental orthopedic diseases by providing a non-invasive method to evaluate the vascular supply and associated pathology of the AECC. 191 VERIFICATION OF THREE DIFFERENT MMP-13 ISOFORMS EXPRESSION IN HUMAN OSTEOARTHRITIC CARTILAGE A. Farran y, L. Tio y, J. Monfort y, J.-P. Pelletier z, J. Martel-Pelletier x. y IMIM-Hosp. del Mar, Barcelona, Spain; zCtr. Hosp.ier de l'Universite de Montreal, Montreal, Montreal, QC, Canada; xDept. of Pharmacology, Dept. of Med., Montreal, QC, Canada Purpose: Collagenase-3 (MMP-13) is a human matrix metalloproteinase highly overexpressed in diseases where tissue repair and remodelling is needed, such as rheumatoid arthritis (RA), osteoarthritis (OA) and some cancers. However, its expression in normal tissues is limited to fetal ossification processes. MMP-13 can digest fibrillar collagen, preferentially type II collagen, but also glomerular collagens and other components of the extracellular matrix (ECM). MMP-13 structures is composed of 4 domains: a hydrophobic pre-domine necessary for the secretion, a pro-domain involved in enzyme latency, a catalytic domain, and a hemopexin-like domain This last is essential for the substrate recognition and collagenolytic activity. Three different MMP-13 transcripts of 3.0, 2.5 and 2.2/2.0 kb have been described to be expressed in human cells. The 2.5kb transcript (isoform 205) corresponds to the MMP-13 original form, while the 3.0kb transcript (isoform 344) presents an insertion at the C-terminal produced by lack of exon 9B splicing. Finally, the smaller transcript of 2.2/2.0kb (isoform 209) presents a deletion (probably due to alternative splicing) of 88 amino acids, also affecting the C-terminal domain. Our objective is to demonstrate the presence of these three MMP13 protein isoforms in human OA samples. Methods: A specific peptide from each isoform was synthesized and two rabbits were immunized with each peptide. The antibodies recognizing each isoform were purified from the total antiserum by sulfolink column. On the other hand MMP-13 isoforms were synthetized in vitro in a Sf9 insect cells system, with a recombinant baculovirus containing MMP-13 transcripts cloned. The insect cells were culture to produce the respective isoforms, and they were purified by molecular exclusion chromatography. These proteins were used to test the specificity of the polyclonal antibodies obtained by Western Blot. Finally, ECM proteins were extracted from cartilage samples obtained from knee and hip arthrosic patients undergoing arthroplasty, using Guanidinium chloride (4M) method. The presence of the 3 isoforms in these samples was assay by western blot with the specific isoform polyclonal antibodies obtained. Results: The purified polyclonal antibodies show immunoreactivity only in front of its specific isoform, showing that they are useful for the detection of each specific isoform in the samples. In all the samples tested, different intensities of the bands corresponding of each antibody were detected. No relative quantification could be performed due to the lack of a standard of each MMP-13 isoforms that allows us to compare the affinity of each polyclonal antibody to each specific isoform. Conclusions: The MMP-13 mRNA isoforms are translated to protein in cartilage OA samples. The transcripts containing the deleted and the alternatively spliced exons differ from the original sequence in the region coding for the hemopexin-like domain. This domain is necessary to cleave native triple helical collagens and provide to the protease its substrate specificity and affinity. The expression of 209 and 344 isoform could have clinical implications in OA if they present different subtracted recognition and/or speed of degradation, explaining some differences observed in the pathophysiology of the disease. 192 QUANTITATIVE ECHOGENICITY OF SMALL INTRA-ARTICULAR DEPOSITS OF CALCIUM, HYALINE CARTILAGE THICKNESS AND SONOGRAPHIC ASPECTS OF THE SYNOVIUM IN PATIENTS WITHOUT RADIOGRAPHIC CHONDROCALCINOSIS A. Checa y, H. Hussain y, E. Russell z. yDrexel Univ. Coll. of Med., Philadelphia, PA, USA; zChristiana Care Hlth.System, Newark, DE, USA Purpose: Ultrasonography is very helpful in the detection of intraarticular crystal deposits and also in distinguishing gout from chondrocalcinosis (CC). However, only three patients without CC on radiographies with evidence of calcium deposits within the cartilage detected by ultrasound (US) have been reported. Methods: In a cohort of 406 patients who underwent musculoskeletal US from January 2010 to June 2011, 30 patients with chondrocalcinosis were identified by the presence of calcium deposits using a machine equipped with an 8-13 MHz linear transducer. The presence of chondrocalcinosis was sonographically recognized as hyperechoic foci within the articular cartilage or fibrocartilage. Once aggregates of calcium were identified, the size was measured unless the deposit burden was too large to quantify. The quantitative echogenicity was assessed among all patients with chondrocalcinosis. A sampling of the area of the calcium aggregates with apparent highest echogenicity was matched with the gray scale bar and measured in a scale of 0 to 10 centimeters. In addition, cartilage thickness was measured on transverse view obtained with the knee fully flexed. In the same view, a minimal-crystal distance of the deposit (distance of the superior margin of the deposit to the cartilage surface) was calculated. Results: We identified 30 patients with US evidence of aggregates of calcium within the wrist or knee cartilage. Two patients were excluded from the study since prior radiographs of the joint were not available. Of the 28 patients included in the study, 9 (32%) showed radiographic evidence of chondrocalcinosis and 19 (68%) patients had no evidence of chondrocalcinosis on prior radiographs (p 1⁄4 0.001).Those patients with sonographic, but not radiographic CC, predominately had small calcium deposition [mean: 1.5mm (range: 0.8mm4.6mm)] vs. the group with radiographic CC that showed extensive deposition (Panel A). The group with radiographic CC showed deposits in more than one compartment (82%), which was observed in only 33% in the group with no radiographic CC. The patients with CC on x-ray had deposits with higher echogenicity (mean: 6.2) compared with those without (mean: 5.7). However, it was not statistically significant (p1⁄40.16). Cartilage thickness was not different between patients with or without radiographic CC [mean: 1.96mm vs. 2.0mm respectively, p1⁄40.84]. Patients without radiographic CC showed a small minimal-crystal distance [mean: 0.5 mm (range: 0-1.3mm)] compared with the group with CC on radiographies [mean: 0.8mm (range: 0.3-1.6)]. In the first group (21 knees), this distance was similar in presence or not of non-shadowing hyperechoic dots within the synovium or effusion [mean: 0.5mm vs. 0.4 mm, p1⁄40.25]. Effusion and synovial hypertrophy were detected in the majority of patients irrespective of the presence of small or extensive deposits of calcium. Roughly one-third of all patients showed hyperechoic dots within the synovium. The presence of dots within the effusion was detected in 42% in the group with occult CC vs. 33% with radiographic CC (Panel B, C and D). Ultimately, a calcified meniscus was identified in 26% of patients without radiographic CC. Conversely, all patients with radiographic evidence of CC showed a meniscocalcinosis sonographically (Panel B). Conclusions: Ultrasound was better than convectional radiography in detecting small deposits of calcium within the cartilage. Knee cartilage thickness was similar in both groups with and without radiographic CC. We speculate that small size of the calcium deposits, mainly localized in one compartment of the knee, lower echogenicity, and the low rate of

Articular cartilage assessment in femoroacetabular impingement (FAI) is challenging. Recent studies on T2* relaxation time mapping suggest the technique may be useful in diagnosing cartilage damage. The purpose of this case report is to describe how quantitative T2*-mapping may improve cartilage assessment of the acetabulum in patients with FAI. MR arthrography was performed at 3 Tesla (T) using intra-articular Gadolinium and a T2* mapping protocol. Data from the acetabular cartilage were separated from femoral head cartilage data and then superimposed on a flattened, map-projection representation of the patient's acetabulum. The areas of unhealthy cartilage observed at the time of arthroscopy – including debonding and delamination – were seen preoperatively at the same anatomic locations as areas of decreased T2* values. T2* mapping values provided a non-invasive assessment of the acetabular articular cartilage. A flattened acetabular map projection allowed for anatomic visualization of areas of unhealthy cartilage. Level of evidence Level IV.

The dorsal stream is a dominant visuomotor pathway that connects the striate and extrastriate cortices to posterior parietal areas. In turn, the posterior parietal areas send projections to the frontal primary motor and premotor areas. This cortical pathway is hypothesized to be involved in the transformation of a visual input into the appropriate motor output. In this study we used functional magnetic resonance imaging (fMRI) of the entire brain to determine the patterns of activation that occurred while subjects performed a visually guided motor task. In nine human subjects, fMRI data were acquired on a 4-T whole-body MR system equipped with a head gradient coil and a birdcage RF coil using a T * 2 -weighted EPI sequence. Functional activation was determined for three different tasks: (1) a visuomotor task consisting of moving a cursor on a screen with a joystick in relation to various targets, (2) a hand movement task consisting of moving the joystick without visual input, and (3) a eye movement task consisting of moving the eyes alone without visual input. Blood oxygenation level-dependent (BOLD) contrast-based activation maps of each subject were generated using period cross-correlation statistics. Subsequently, each subject's brain was normalized to Talairach coordinates, and the individual maps were compared on a pixel by pixel basis. Significantly activated pixels common to at least four out of six subjects were retained to construct the final functional image. The pattern of activation during visually guided movements was consistent with the flow of information from striate and extrastriate visual areas, to the posterior parietal complex, and then to frontal motor areas. The extensive activation of this network and the reproducibility among subjects is consistent with a role for the dorsal stream in transforming visual information into motor behavior. Also extensively activated were the medial and lateral cerebellar structures, implicating the cortico–ponto–cerebellar pathway in visually guided movements. Thalamic activation, particularly of the pulvinar, suggests that this nucleus is an important subcortical target of the dorsal stream.

Introduction The causes of low back pain (LBP) are poorly defined and indistinct; the most often implicated tissue as the origin for pain is the intervertebral disk (IVD)1,2. Traditionally, lumbar spine range of motion measurements and IVD gross morphology (from MR images) are used to assess spinal health, but largely fail to correlate well with pain or provide clinically useful patient stratification3,4,5. Due to the inadequacies of current imaging techniques in differentiating symptomatic versus nonsymptomatic changes, a new series of quantitative protocols is emerging6. Quantitative T2* relaxation time measurements probe biochemical properties of the tissues. T2* mapping techniques are employed for cartilage assessment, probing spatial collagen architecture in conjunction with water molecule mobility7. As a first step, the goal of this work is to correlate quantitative MR mapping of the IVD with 3D kinematic data to probe the relationship between disk biochemical properties and functional kinematic parameters. Materials and Methods Total 18 osteoligamentous cadaveric lumbar spines (L3-S1), acquired from the UofM Bequest Program (aveage: 53.2 ± 15.5 years; range: 21 to 71 years) were examined using conventional and quantitative MR imaging protocols and biomechanically exercised in the cardinal planes. MR imaging was performed on a Siemens 3T scanner (Magnetom Trio; Siemens Health care). Conventional T2-weighted sagittal anatomic images were acquired for Pfirrmann disk grading (Fig. 1A)8. T2* relaxation maps were obtained using [TR(ms): 500; TE(ms): 4.18, 11.32, 18.46, 25.60, 32.74, 39.88; Voxel Size(mm): 0.5 × 0.5 × 3.0, Slices: 33]. Quantitative T2* maps were calculated (MapIt, Siemens Health care) and mean T2* values were recorded using Osirix Imaging Software across five regions of interest (ROI) (Fig. 1B). Utilizing MATLAB (Mathworks Inc. Natick, MA), the central ROI mean relaxation value was evaluated in the coronal plane as the intensity changed from lateral to medial to lateral (Fig. 1C). Using a least squares method, the slope of the transition zone (ms/mm) between the annulus fibrosus and nucleus pulposus on each side was computed (Fig. 1D). The area underneath the curve was calculated and normalized to the width of the IVD (Fig. 1D). After imaging, the specimens were embedded in polymethylmethacrylate and tested in a six-axis Spine Kinetic Simulator (8821 Biopuls, Instron, Norwood, MA, USA). Pure moments of up to 7 Nm were applied sinusoidally (0.015 Hz). Three cycles were performed and the final cycle was analyzed. Load and moment data was collected at 100 Hz. Segmental displacements were recorded using a 3D visual motion analysis 5-camera system (Vicon MX-F40NIR, Vicon Motion Systems, Centennial, CO) capturing a four-ball infrared reflecting marker set attached to each vertebral body. Kinematic outcomes (ROM, Neutral Zone, NZ/ROM, Stiffness) were correlated with imaging parameters using Pearson correlation test with alpha acceptance of 0.05. Results The T2* relaxation measurements in the nucleus pulposus were significantly correlated with flexion stiffness ( p = 0.024) and lateral bending stiffness ( p = 0.021) wherein increased stiffness was associated with lower signal and higher Pfirrmann grade. The slope of the transition zone for the 54 disk samples was found to be correlated with the flexion stiffness ( p = 0.026), flexion range of motion ( p = 0.002), lateral bending stiffness ( p = 0.029), and lateral bending range of motion ( p = 0.0028). The area under the T2* intensity curves in the coronal plane was likewise found to be significantly correlated with following biomechanical measures: flexion stiffness ( p = 0.043), flexion range of motion (p = 0.014), lateral bending stiffness (p = 0.021), and lateral bending range of motion ( p = 0.023). Conclusion MR imaging of IVD using T2* relaxation measurements provide quantitative assessment of the disk's biochemical properties which is related to its biomechanical competence. This new methodology and analysis technique may provide enhanced quantitative data on the degenerative cascade which alters disk function and in some cases leads to painful outcomes. Limitations of this research include the biomechanical testing of cadaveric samples without musculature and their postmortem imaging at room temperature. Next, we aim to evaluate this relationship in human subjects and determine its clinical efficacy. This research linked kinematic data with quantitative T2* mapping of IVD from across the degenerative spectrum. By coupling quantitative MR imaging with functional kinematic outcomes, these data may improve patient stratification and targeted therapeutic intervention for patients suffering from LBP. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Salminen. Spine 1999 Cheung. Spine 2009 Boden. Journal of Joint and Bone surgery 1990 Savage. Spine Journal 1997 Mimura. Spine 1994 Welsch. Skeletal Radiology 2011 Mamisch. Skeletal Radiology 2011 Pfirrmann. Spine 2001. Funding: NIH/NIAMS T32 AR050938

Publisher Summary Evolution of magnetic resonance imaging (MRI) has resulted in visualization of the anatomical structures in the living human brain with high spatial resolution and contrast. The structural information with detail that is evident in such magnetic resonance images has been complemented with biochemical and metabolic information following the development of magnetic resonance spectroscopy methods that provide chemical shift and spatial encoding. The noninvasive nature of these spectroscopic methods has enabled the investigation of intracellular metabolism and bioenergetics in preparations ranging from intact cells in suspension to humans. Among the plethora of biomedical applications with magnetic resonance, an avidly pursued new dimension is the acquisition of physiological information, such as tissue perfusion and function. A recent development in this new dimension is the ability to obtain functional maps that depict regions of the human brain that are activated during the performance of a specific task and permit the investigation of the extraordinary capabilities unique to the human brain. The basic MRI methods under development are blood oxygenation level–dependent (BOLD) contrast imaging, imaging based on first-pass exogenous vascular contrast agents, and blood perfusion imaging using inversion-recovery methods. This chapter focuses on BOLD-based functional brain mapping.

A hemispheric asymmetry in the functional activation of the human motor cortex during contralateral (C) and ipsilateral (I) finger movements, especially in right-handed subjects, was documented with nuclear magnetic resonance imaging at high field strength (4 tesla). Whereas the right motor cortex was activated mostly during contralateral finger movements in both right-handed (C/I mean area of activation = 36.8) and left-handed (C/I = 29.9) subjects, the left motor cortex was activated substantially during ipsilateral movements in left-handed subjects (C/I = 5.4) and even more so in right-handed subjects (C/I = 1.3).

In vivo 1H MRS can be used to detect and quantify the lactate resonance at 1.3 ppm provided that overlapping lipid resonances are eliminated. A homonuclear spectral editing method was developed to acquire uncontaminated 1H spectra of lactate with adiabatic pulses. An advantage of the adiabatic pulse sequence is the ability to induce uniform flip angles and to maximize sensitivity in applications employing surface coil transmitters which produce highly inhomogeneous B1. Glycolytic activity in an intracerebral C6 glioma in rats was monitored by using adiabatic editing sequences to observe [3-13C]lactate produced from infused [1-13C]glucose. Acute hyperglycemia (serum glucose > 22 mM, n = 10) had no significant effect (P = 0.08) on the total ([12C] + [13C]) tumor lactate signal intensity.

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R2*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.

We report the use of high-speed magnetic resonance imaging to follow the changes in image intensity in the human visual cortex during stimulation by a flashing checkerboard stimulus. Measurements were made in a 2.1-T, 1-m-diameter magnet, part of a Bruker Biospec spectrometer that we had programmed to do echo-planar imaging. A 15-cm-diameter surface coil was used to transmit and receive signals. Images were acquired during periods of stimulation from 2 s to 180 s. Images were acquired in 65.5 ms in a 10-mm slice with in-plane voxel size of 6 x 3 mm. Repetition time (TR) was generally 2 s, although for the long flashing periods, TR = 8 s was used. Voxels were located onto an inversion recovery image taken with 2 x 2 mm in-plane resolution. Image intensity increased after onset of the stimulus. The mean change in signal relative to the prestimulation level (delta S/S) was 9.7% (SD = 2.8%, n = 20) with an echo time of 70 ms. Irrespective of the period of stimulation, the increase in magnetic resonance signal intensity was delayed relative to the stimulus. The mean delay measured from the start of stimulation for each protocol was as follows: 2-s stimulation, delay = 3.5 s (SD = 0.5 s, n = 10) (the delay exceeds stimulus duration); 20- to 24-s stimulation, delay = 5 s (SD = 2 s, n = 20).

We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce high-spatial-resolution functional brain maps in humans. Reducing the image-acquisition echo time from 40 msec to 8 msec reduces the amplitude of the fractional signal change, suggesting that it is produced by a change in apparent transverse relaxation time T*2. The amplitude, sign, and echo-time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow and concomitantly increases venous-blood oxygenation.

Summary Increased autophagocytosis in hepatocytes was found in response to conditions of ischaemia/hypoxia. Initial stages proved to be recordable. These were found to become manifest through the formation of phospholipid membrane structures, approximately 5 nm in width, coalescing in circular formations with vesicular extensions. They may further develop to form multilayer myelin structures. Enveloped cytoplasmic regions and organelles were unchanged, at the begining, and subsequently coalesced typically into autophagolysosomes and autophagic vacuoles. Verification will be necessary to find out if these initial stages occur only in response to hypoxia or constitute a phenomenon of general validity.

Summary NMR-spectroscopy and electron microscopy were applied in order to find out whether nephrotoxic effects of cyclosporine A in combination with ischaemia on rat kidney are of significance for the energy metabolism of the organ. CSA was administered in daily doses of 15 mg/kg rat over 20 days. Use was made of the particular advantage of 31P-NMR-spectroscopy to follow up the dynamics of high-energy phosphate concentrations in the same tissue. Ultrastructural changes were observed in the region of the proximal tubule. Some mitochondria showed degenerative changes, others increased density of cristae. The total number of mitochondria was increased. This observation together with the coexistence of vacuolarly degenerated mitochondria and mitochondria with increased activity after CSA treatment is interpreted as expression of a compensatory mechanism that keeps constant the totality of high-energy phosphates despite damage to some mitochondria.

Summary Background Osteochondrosis (OC) is a common developmental orthopedic disease affecting both humans and animals. Despite increasing recognition of this disease among children and adolescents, its pathogenesis is incompletely understood because clinical signs are often not apparent until lesions have progressed to end-stage, and examination of cadaveric early lesions is not feasible. In contrast, both naturally-occurring and surgically-induced animal models of disease have been extensively studied, most notably in horses and swine, species in which OC is recognized to have profound health and economic implications. The potential for a translational model of human OC has not been recognized in the existing human literature. Objective The purpose of this review is to highlight the similarities in signalment, predilection sites and clinical presentation of naturally-occurring OC in humans and animals and to propose a common pathogenesis for this condition across species. Study design Review. Methods The published human and veterinary literature for the various manifestations of OC was reviewed. Peer-reviewed original scientific articles and species-specific review articles accessible in PubMed (US National Library of Medicine) were eligible for inclusion. Results A broad range of similarities exists between OC affecting humans and animals, including predilection sites, clinical presentation, radiographic/MRI changes, and histological appearance of the end-stage lesion, suggesting a shared pathogenesis across species. Conclusion This proposed shared pathogenesis for OC between species implies that naturally-occurring and surgically-induced models of OC in animals may be useful in determining risk factors and for testing new diagnostic and therapeutic interventions that can be used in humans.

Deep learning (DL) has emerged as a tool for improving accelerated MRI reconstruction. A common strategy among DL methods is the physics-based approach, where a regularized iterative algorithm alternating between data consistency and a regularizer is unrolled for a finite number of iterations. This unrolled network is then trained end-to-end in a supervised manner, using fully-sampled data as ground truth for the network output. However, in a number of scenarios, it is difficult to obtain fully-sampled datasets, due to physiological constraints such as organ motion or physical constraints such as signal decay. In this work, we tackle this issue and propose a self-supervised learning strategy that enables physics-based DL reconstruction without fully-sampled data. Our approach is to divide the acquired sub-sampled points for each scan into training and validation subsets. During training, data consistency is enforced over the training subset, while the validation subset is used to define the loss function. Results show that the proposed self-supervised learning method successfully reconstructs images without fully-sampled data, performing similarly to the supervised approach that is trained with fully-sampled references. This has implications for physics-based inverse problem approaches for other settings, where fully-sampled data is not available or possible to acquire., 5 Pages, 5 Figures