Quantitative T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in an in vivo piglet model of Legg-Calvé-Perthes disease.

OBJECTIVE: To determine if the quantitative MRI techniques T2 and T1ρ mapping are sensitive to ischemic injury to epiphyseal cartilage in vivo in a piglet model of Legg-Calvé-Perthes disease using a clinical 3T MRI scanner. We hypothesized that T2 and T1ρ relaxation times would be increased in the epiphyseal cartilage of operated vs contralateral-control femoral heads 1 week following onset of ischemia. DESIGN: Unilateral femoral head ischemia was surgically induced in eight piglets. Piglets were imaged 1 week post-operatively in vivo at 3T MRI using a magnetization-prepared 3D fast spin echo sequence for T2 and T1ρ mapping and a 3D gradient echo sequence for cartilage segmentation. Ischemia was confirmed in all piglets using gadolinium contrast-enhanced MRI. Median T2 and T1ρ relaxation times were measured in the epiphyseal cartilage of the ischemic and control femoral heads and compared using paired t-tests. Histological assessment was performed on a subset of five piglets. RESULTS: T2 and T1ρ relaxation times were significantly increased in the epiphyseal cartilage of the operated vs control femoral heads (ΔT2 = 11.9 ± 3.7 ms, 95% CI = [8.8, 15.0] ms, P < 0.0001; ΔT1ρ = 12.8 ± 4.1 ms, 95% CI = [9.4, 16.2] ms, P < 0.0001). Histological assessment identified chondronecrosis in the hypertrophic and deep proliferative zones within ischemic epiphyseal cartilage. CONCLUSIONS: T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in vivo at clinical 3T MRI. These techniques may be clinically useful to assess injury and repair to the epiphyseal cartilage to better stage the extent of ischemic damage in Legg-Calvé-Perthes disease.

MRI evaluation of articular cartilage in patients with juvenile osteochondritis dissecans (JOCD) using T2∗ mapping at 3T.

OBJECTIVE: Evaluate articular cartilage by magnetic resonance imaging (MRI) T2∗ mapping within the distal femur and proximal tibia in adolescents with juvenile osteochondritis dissecans (JOCD). DESIGN: JOCD imaging studies acquired between August 2011 and February 2019 with clinical and T2∗ mapping MRI knee images were retrospectively collected and analyzed for 31 participants (9F/22M, 15.0 ± 3.8 years old) with JOCD lesions in the medial femoral condyle (MFC). In total, N = 32 knees with JOCD lesions and N = 14 control knees were assessed. Mean T2∗ values in four articular cartilage regions-of-interest (MFC, lateral femoral condyle (LFC), medial tibia (MT), and lateral tibia (LT)) and lesion volume were measured and analyzed using Wilcoxon-rank-sum tests and Spearman correlation coefficients (R). RESULTS: Mean ± standard error T2∗ differences observed between the lesion-sided MFC and the LFC in JOCD-affected knees (28.5 ± 0.9 95% confidence interval [26.8, 30.3] vs 26.3 ± 0.7 [24.8, 27.7] ms, P = 0.088) and between the affected- and control-knee MFC (28.5 ± 0.9 [26.8, 30.3] vs 28.5 ± 0.6 [27.1, 29.9] ms, P = 0.719) were nonsignificant. T2∗ was significantly increased in the lesion-sided MT vs the LT for the JOCD-affected knees (21.5 ± 0.7 [20.1, 22.9] vs 18.0 ± 0.7 [16.5, 19.5] ms, P = 0.002), but this same difference was also observed between the MT and LT in control knees (21.0 ± 0.6 [19.7, 22.3] vs 18.1 ± 1.1 [15.8, 20.4] ms, P = 0.037). There was no significant T2∗ difference between the affected- and control-knee MT (21.5 ± 0.7 [20.1, 22.9] vs 21.0 ± 0.6 [19.7, 22.3] ms, P = 0.905). T2∗ within the lesion-sided MFC was not correlated with patient age (R = 0.20, P = 0.28) or lesion volume (R = 0.06, P = 0.75). T2∗ values were slightly increased near lesions in later-stage JOCD subjects but without statistical significance. CONCLUSIONS: T2∗ relaxations times were not significantly different from control sites in the articular cartilage overlying JOCD lesions in the MFC or adjacent MT cartilage in early-stage JOCD.

Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis.

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.

Activation of visuomotor systems during visually guided movements: a functional MRI study.

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 T2*-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-pontocerebellar pathway in visually guided movements. Thalamic activation, particularly of the pulvinar, suggests that this nucleus is an important subcortical target of the dorsal stream.

Functional magnetic resonance imaging of cerebellar activation during the learning of a visuomotor dissociation task.

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.

Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and handedness.

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).

Localized detection of glioma glycolysis using edited 1H MRS.

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.

Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model.

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.

Functional imaging of human motor cortex at high magnetic field.

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.

Functional brain mapping using magnetic resonance imaging. Signal changes accompanying visual stimulation.

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.

Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging.

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).

Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging.

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.