Interval changes of histogram-derived diffusion indices predict treatment response to induction chemotherapy in head and neck cancer: a feasibility study.

Background: This retrospective study investigated whether the interval change of apparent diffusion coefficient (∆ADC) [baseline and after the first cycle of induction chemotherapy (ICT)] can be used as a valid predictive imaging biomarker of the treatment response to ICT in head and neck cancer (HNC). Methods: A total of 19 consecutive patients with HNC who underwent diffusion-weighted magnetic resonance imaging (DWI) at baseline and after the first cycle of ICT were included. Whole-tumor ADC histogram parameters (mean, median, kurtosis, skewness, entropy, minimal, maximum, 25th percentile, and 75th percentile) were obtained. The correlations of ∆ADC histogram parameters, volume, T-stage, N-stage, and age with the treatment response were examined using the Mann-Whitney U test. The predictive value of histogram parameters was examined using receiver operating characteristic (ROC) curves. Results: Responders showed significantly higher values of ∆ADC25 (0.19±0.23) and ∆ADCmin (1.78±2.98) than non-responders (-0.09±0.15 and -0.73±0.36; P=0.035 and 0.009, respectively). When ∆ADC25 and ∆ADCmin were used for predicting the treatment response, the area under the ROC curve was 0.850/0.933 with a sensitivity of 73.3%/80.0% and specificity of 100%/100% (P=0.036 and 0.009, respectively). Conclusions: ∆ADC25 and ∆ADCmin derived from whole-tumor histogram analysis are valuable imaging biomarkers for the early prediction of the ICT response in HNC.

Radial T2* mapping reveals early meniscal abnormalities in patients with knee osteoarthritis.

OBJECTIVE: We aimed to validate a 2D radial T2* mapping method and its ability to reveal subtle alterations in the menisci of patients with knee osteoarthritis (OA). METHODS: Of 40 enrolled participants, 20 were diagnosed with OA, and 20 were age- and sex-matched asymptomatic controls. Data from the right knee of each participant were collected using a 1.5-T MRI equipped with a single-channel knee coil. T2* values were acquired using a conventional T2* mapping protocol and a radial T2* mapping method. Mean T2* values in the meniscal white zones, meniscal red zones, and total menisci were calculated. Numerical simulation was performed for validation. RESULTS: Both simulation and clinical data confirmed that 2D radial T2* mapping provided better discrimination than the conventional method. Compared to controls, the OA group showed significantly greater mean (standard deviation) T2* values in the white zones (9.33 [2.29] ms vs. 6.04 [1.05] ms), red zones (9.18 [2.03] ms vs. 6.81 [1.28] ms), and total menisci (9.26 [2.06] ms vs. 6.34 [1.14] ms). Correlations were found between the Lequesne index and the meniscal T2* values in all three regions (r = 0.528, p = 0.017; r = 0.635, p = 0.003; and r = 0.556, p = 0.011, respectively). CONCLUSION: These findings indicate that in early OA, radial T2* mapping is an alternative means of assessing meniscal degeneration and can be used to monitor its progression. KEY POINTS: • Radial T2* mapping outperforms Cartesian T2* mapping. • Radial T2* measurements are useful in assessing meniscal degeneration. • Meniscal T2* values correlate well with disease severity.

Ergosta-7,9(11),22-trien-3ß-ol Alleviates Intracerebral Hemorrhage-Induced Brain Injury and BV-2 Microglial Activation.

Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by an exacerbation of neuroinflammation and neuronal injury, for which few effective therapies are available at present. Inhibition of excessive neuroglial activation has been reported to alleviate ICH-related brain injuries. In the present study, the anti-ICH activity and microglial mechanism of ergosta-7,9(11),22-trien-3ß-ol (EK100), a bioactive ingredient from Asian medicinal herb Antrodia camphorate, were evaluated. Post-treatment of EK100 significantly attenuated neurobehavioral deficit and MRI-related brain lesion in the mice model of collagenase-induced ICH. Additionally, EK100 alleviated the inducible expression of cyclooxygenase (COX)-2 and the activity of matrix metalloproteinase (MMP)-9 in the ipsilateral brain regions. Consistently, it was shown that EK100 concentration-dependently inhibited the expression of COX-2 protein in Toll-like receptor (TLR)-4 activator lipopolysaccharide (LPS)-activated microglial BV-2 and primary microglial cells. Furthermore, the production of microglial prostaglandin E2 and reactive oxygen species were attenuated by EK100. EK100 also attenuated the induction of astrocytic MMP-9 activation. Among several signaling pathways, EK100 significantly and concentration-dependently inhibited activation of c-Jun N-terminal kinase (JNK) MAPK in LPS-activated microglial BV-2 cells. Consistently, ipsilateral JNK activation was markedly inhibited by post-ICH-treated EK100 in vivo. In conclusion, EK100 exerted the inhibitory actions on microglial JNK activation, and attenuated brain COX-2 expression, MMP-9 activation, and brain injuries in the mice ICH model. Thus, EK100 may be proposed and employed as a potential therapeutic agent for ICH.

Diffusion Tensor Imaging of the Spinal Cord.

Spinal cord often is regarded as one of the last territories in the central nervous system where diffusion tensor imaging (DTI) can be used to probe white matter architecture. This article reviews current progress in spinal cord DTI, starting with anatomic properties and technical challenges that make spinal cord DTI a difficult task. Several possibilities offered by advanced pulse sequences that might overcome the difficulties are addressed, with associated trade-offs and limitations. Potential clinical assistance also is discussed in various spinal cord pathologies, such as myelopathy due to external compression, spinal cord tumors, acute ischemia, traumatic injury, and so forth.

The value of MR T2* measurements in normal and osteoarthritic knee cartilage: effects of age, sex, and location.

OBJECTIVES: Our aim was to investigate the role of age, sex, and location on MR T2* values of the knee cartilage in asymptomatic controls and patients with osteoarthritis (OA). METHODS: A total of 100 participants, including 40 with OA and 60 asymptomatic controls, were enrolled in this study. Patients with OA were compared to age- (≥ 41 years old) and sex-matched controls. Controls were divided by age (aged 21-40 years, 41-60, ≥ 61). T2* values were acquired using a T2*-weighted fast gradient-echo sequence and a 1.5-T MRI scanner. T2* values of the femoral and tibial cartilages at the weight-bearing areas were obtained for comparisons. RESULTS: The T2* values significantly increased with age and were significantly higher in the medial femoral cartilage (35.96 ± 4.06 and 31.85 ± 2.44 ms), medial tibial cartilage (30.95 ± 2.87 and 28.24 ± 1.74 ms), and lateral femoral cartilage (33.90 ± 3.15 and 31.51 ± 2.28 ms) in OA patients versus age- and sex-matched controls. Among OA patients, the T2* values for women exceed those in men in the medial femoral cartilage (37.59 ± 4.43 and 34.16 ± 2.63 ms) and medial tibial cartilage (32.17 ± 2.59 and 29.62 ± 2.53 ms; p < 0.01). Correlations were found between the Lequesne index and the T2* values for the medial femoral cartilage (r = 0.636, p < 0.001) and the medial tibial cartilage (r = 0.433, p = 0.005). CONCLUSION: Cartilage T2* values tend to increase with age and are useful in assessing cartilage degeneration in early OA. KEY POINTS: • Age, sex, and location have important effects on cartilage T2* values at the knee. • MR T2* measurements are useful toward assessing cartilage degeneration. • The medial femoral and tibial cartilage T2* values correlate well with disease severity.

Machine Learning-Based Radiomics for Molecular Subtyping of Gliomas.

Purpose: The new classification announced by the World Health Organization in 2016 recognized five molecular subtypes of diffuse gliomas based on isocitrate dehydrogenase (IDH) and 1p/19q genotypes in addition to histologic phenotypes. We aim to determine whether clinical MRI can stratify these molecular subtypes to benefit the diagnosis and monitoring of gliomas.Experimental Design: The data from 456 subjects with gliomas were obtained from The Cancer Imaging Archive. Overall, 214 subjects, including 106 cases of glioblastomas and 108 cases of lower grade gliomas with preoperative MRI, survival data, histology, IDH, and 1p/19q status were included. We proposed a three-level machine-learning model based on multimodal MR radiomics to classify glioma subtypes. An independent dataset with 70 glioma subjects was further collected to verify the model performance.Results: The IDH and 1p/19q status of gliomas can be classified by radiomics and machine-learning approaches, with areas under ROC curves between 0.922 and 0.975 and accuracies between 87.7% and 96.1% estimated on the training dataset. The test on the validation dataset showed a comparable model performance with that on the training dataset, suggesting the efficacy of the trained classifiers. The classification of 5 molecular subtypes solely based on the MR phenotypes achieved an 81.8% accuracy, and a higher accuracy of 89.2% could be achieved if the histology diagnosis is available.Conclusions: The MR radiomics-based method provides a reliable alternative to determine the histology and molecular subtypes of gliomas. Clin Cancer Res; 24(18); 4429-36. ©2018 AACR.

Changes in sensorimotor-related thalamic diffusion properties and cerebrospinal fluid hydrodynamics predict gait responses to tap test in idiopathic normal-pressure hydrocephalus.

OBJECTIVES: To compare diffusion tensor (DT)-derived indices from the thalamic nuclei and cerebrospinal fluid (CSF) hydrodynamic parameters for the prediction of gait responsiveness to the CSF tap test in early iNPH patients. METHODS: In this study, 22 patients with iNPH and 16 normal controls were enrolled with the approval of an institutional review board. DT imaging and phase-contrast magnetic resonance imaging were performed in patients and controls to determine DT-related indices of the sensorimotor-related thalamic nuclei and CSF hydrodynamics. Gait performance was assessed in patients using gait scale before and after the tap test. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were applied to compare group differences between patients and controls and assess the predictive performance of gait responsiveness to the tap test in the patients. RESULTS: Fractional anisotropy (FA) and axial diffusivity showed significant increases in the ventrolateral (VL) and ventroposterolateral (VPL) nuclei of the iNPH group compared with those of the control group (p < 0.05). The predictions of gait responsiveness of ventral thalamic FA alone (area under the ROC curve [AUC] < 0.8) significantly outperformed those of CSF hydrodynamics alone (AUC < 0.6). The AUC curve was elevated to 0.812 when the CSF peak systolic velocity and FA value were combined for the VPL nucleus, yielding the highest sensitivity (0.769) and specificity (0.778) to predict gait responses. CONCLUSIONS: Combined measurements of sensorimotor-related thalamic FA and CSF hydrodynamics can provide potential biomarkers for gait response to the CSF tap test in patients with iNPH. KEY POINTS: • Ventrolateral and ventroposterolateral thalamic FA may predict gait responsiveness to tap test. • Thalamic neuroplasticity can be assessed through DTI in idiopathic normal-pressure hydrocephalus. • Changes in the CST associated with gait control could trigger thalamic neuroplasticity. • Activities of sensorimotor-related circuits could alter in patients with gait disturbance. • Management of patients with iNPH could be more appropriate.

Histogram analysis of T2*-based pharmacokinetic imaging in cerebral glioma grading.

BACKGROUND AND OBJECTIVE: To investigate the feasibility of histogram analysis of the T2*-based permeability parameter volume transfer constant (Ktrans) for glioma grading and to explore the diagnostic performance of the histogram analysis of Ktrans and blood plasma volume (vp). METHODS: We recruited 31 and 11 patients with high- and low-grade gliomas, respectively. The histogram parameters of Ktrans and vp, derived from the first-pass pharmacokinetic modeling based on the T2* dynamic susceptibility-weighted contrast-enhanced perfusion-weighted magnetic resonance imaging (T2* DSC-PW-MRI) from the entire tumor volume, were evaluated for differentiating glioma grades. RESULTS: Histogram parameters of Ktrans and vp showed significant differences between high- and low-grade gliomas and exhibited significant correlations with tumor grades. The mean Ktrans derived from the T2* DSC-PW-MRI had the highest sensitivity and specificity for differentiating high-grade gliomas from low-grade gliomas compared with other histogram parameters of Ktrans and vp. CONCLUSIONS: Histogram analysis of T2*-based pharmacokinetic imaging is useful for cerebral glioma grading. The histogram parameters of the entire tumor Ktrans measurement can provide increased accuracy with additional information regarding microvascular permeability changes for identifying high-grade brain tumors.

Assessing the selective therapeutic efficacy of superparamagnetic erlotinib nanoparticles in lung cancer by using quantitative magnetic resonance imaging and a nuclear factor kappa-B reporter gene system.

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E NPs) as theranostic probe that can potentially provide a new avenue for monitoring drug delivering through noninvasive magnetic resonance imaging. MRI ΔR2* relaxivity measurements offer an opportunity to quantitatively evaluate the uptake of FeDC-E NPs at cellular and tumoral levels. Additionally, NF-κB reporter gene system provides NF-κB activation status monitoring to validate the therapeutic efficiency of FeDC-E NPs. FeDC-E NPs not only inhibit the tumor growth and NF-κB-modulated antiapoptotic mechanism but also trigger extrinsic and intrinsic apoptotic pathways. Taken together, dual functional FeDC-E NPs offer diagnostic and therapeutic benefits against lung cancers, indicating that our presented probe could be applied in clinical.

Identification of epidermal growth factor receptor-positive glioblastoma using lipid-encapsulated targeted superparamagnetic iron oxide nanoparticles in vitro.

BACKGROUND: Targeted superparamagnetic iron oxide (SPIO) nanoparticles have emerged as a promising biomarker detection tool for molecular magnetic resonance (MR) image diagnosis. To identify patients who could benefit from Epidermal growth factor receptor (EGFR)-targeted therapies, we introduce lipid-encapsulated SPIO nanoparticles and hypothesized that anti-EGFR antibody cetuximab conjugated of such nanoparticles can be used to identify EGFR-positive glioblastomas in non-invasive T2 MR image assays. The newly introduced lipid-coated SPIOs, which imitate biological cell surface and thus inherited innate nonfouling property, were utilized to reduce nonspecific binding to off-targeted cells and prevent agglomeration that commonly occurs in nanoparticles. RESULTS: The synthesized targeted EGFR-antibody-conjugated SPIO (EGFR-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, gel electrophoresis mobility shift assays, transmission electron microscopy (TEM) images, and cell line affinity assays, and the results showed that the conjugation was successful. The targeting efficiency of the synthesized EGFR-SPIO nanoparticles was confirmed through Prussian blue staining and TEM images by using glioblastoma cell lines with high or low EGFR expression levels. The EGFR-SPIO nanoparticles preferentially targeted U-251 cells, which have high EGFR expression, and were internalized by cells in a prolonged incubation condition. Moreover, the T2 MR relaxation time of EGFR-SPIO nanoparticles could be used for successfully identifying glioblastoma cells with elevated EGFR expression in vitro and distinguishing U-251 cells from U-87MG cells, which have low EFGR expression. CONCLUSION: These findings reveal that the lipid-encapsulated EGFR-SPIO nanoparticles can specifically target cells with elevated EGFR expression in the three tested human glioblastoma cell lines. The results of this study can be used for noninvasive molecular MR image diagnosis in the future.

Early white matter injuries in patients with acute carbon monoxide intoxication: A tract-specific diffusion kurtosis imaging study and STROBE compliant article.

Evaluation of acute white matter injuries caused by carbon monoxide (CO) poisoning can be limited by conventional magnetic resonance (MR) imaging. We aim to evaluate the feasibility of diffusion kurtosis imaging (DKI) for early detection of white matter alterations in patients with acute CO intoxication.A total of 30 subjects including 15 acute CO patients and 15 age- and sex-matched healthy volunteers were enrolled in this study. MR examinations were performed on a 3T MR scanner within 8 days after CO intoxication. DKI data were acquired to derive axial, radial, and mean kurtosis, as well as fractional anisotropy (FA), axial, radial, and mean diffusivity for tract-specific comparisons between the 2 groups.Significant decreases of mean kurtosis were shown in the genu of corpus callosum, cingulum, and motor-related tracts (corticospinal and corticobulbar tracts) in patients with acute CO intoxication as compared with controls. On the contrary, significant differences of FA values were merely shown in the regions of corticospinal tracts.DKI demonstrated comparably stronger potential than diffusion tensor imaging in terms of early detection of white matter changes in patients with acute CO intoxication. This may have implications in therapeutic strategy for managing acute CO intoxication patients.

Middle Cerebral Artery Calcification: Association With Ischemic Stroke.

Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93-14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification.

High Agatston Calcium Score of Intracranial Carotid Artery: A Significant Risk Factor for Cognitive Impairment.

The effect of intracranial internal carotid artery (ICA) calcification on cognitive impairment is uncertain. Our objective was to investigate whether intracranial ICA calcification is a significant cognitive predictor for cognitive impairment. Global cognition and degrees of intracranial ICA calcification of 579 subjects were assessed with Mini-Mental State Examination (MMSE) and Agatston calcium scoring method, respectively. Other risk factors for cognitive impairment, including age, education level, hypertension, diabetes mellitus, smoking, hyperlipidemia, and body mass index, were documented and analyzed for their associations with cognitive function. In univariate analyses, older age, lower education level, hypertension, diabetes mellitus, and higher intracranial ICA Agatston scores were significantly associated with cognitive impairment. In ordinal logistic regression, only age and total intracranial ICA Agatston score were significant risk factors for cognitive impairment. After adjustment for the other documented risk factors, subjects were 7% (95% CI: 5-10; P < 0.001) and 6% (95% CI: 0-13; P = 0.04) more likely to have lower cognitive category with every year increment of age and every 100-point increment of the total intracranial ICA Agatston score respectively. These results suggest an important role of the intracranial ICA calcification on cognitive impairment.

Prominent vessel sign on susceptibility-weighted imaging in acute stroke: prediction of infarct growth and clinical outcome.

BACKGROUND AND PURPOSE: Predicting the risk of further infarct growth in stroke patients is critical to therapeutic decision making. We aimed to predict early infarct growth and clinical outcome from prominent vessel sign (PVS) identified on the first susceptibility-weighted image (SWI) after acute stroke. MATERIALS AND METHODS: Twenty-two patients with middle cerebral artery (MCA) infarction had diffusion-weighted imaging, SWI, MR angiography, and clinical evaluation using the National Institutes of Health Stroke Scale at 7-60 hours and 5-14 days after stroke onset. Late-stage clinical evaluation at 1 and 3 months used the modified Rankin Scale. The infarct area and growth were scored from 10 (none) to 0 (infarct or growth in all 10 zones) using the Alberta Stroke Program Early CT Score (ASPECTS) system. RESULTS: Infarct growth on the second MRI occurred in 13 of 15 patients with PVS on the first MRI and not in any patient without PVS (n=7; r=0.86, P<0.001). The extent of PVS was significantly correlated with infarct growth (r=0.82, P<0.001) and early-stage outcome (P=0.02). No between-group difference in late-stage clinical outcome was found. CONCLUSION: PVS on the first SWI after acute MCA territory stroke is a useful predictor of early infarct growth. Extensive PVS within the large MCA territory is related to poor early-stage outcome and could be useful for clinical assessment of stroke.

Change in T2* relaxation time of Hoffa fat pad correlates with histologic change in a rat anterior cruciate ligament transection model.

The Hoffa fat pad (infrapatellar fat pad) is a source of post-traumatic anterior knee pain, and Hoffa disease is a syndrome leading to chronic inflammation of the fat pad. Herein, change in T2* relaxation time of the fat pad was measured in a rodent anterior cruciate ligament transection (ACLX) model in order to (i) examine the causal relationship of anterior cruciate ligament (ACL) deficiency and Hoffa disease and (ii) demonstrate the feasibility of using T2* as an imaging biomarker to monitor disease progression. Three groups of male Sprague Dawley rats (n = 6 each group), received either (i) no intervention; (ii) sham surgery at the right knee; or (iii) right ACLX. T2* relaxation time was measured and histology was examined in the Hoffa fat pad after surgery. At 13 and 18 weeks after surgery, T2* values were significantly higher in the right fat pad than the left (p < 0.001) and significantly higher in the ACLX group than the control and sham groups (p < 0.001). Histology showed fibrosis and degeneration of adipocytes in the right knees of the ACLX group. We conclude that ACL deficiency and Hoffa disease are causally related and that MRI T2* value can serve as an imaging biomarker of Hoffa disease progression.

High spatial resolution brain functional MRI using submillimeter balanced steady-state free precession acquisition.

PURPOSE: One of the technical advantages of functional magnetic resonance imaging (fMRI) is its precise localization of changes from neuronal activities. While current practice of fMRI acquisition at voxel size around 3 × 3 × 3 mm(3) achieves satisfactory results in studies of basic brain functions, higher spatial resolution is required in order to resolve finer cortical structures. This study investigated spatial resolution effects on brain fMRI experiments using balanced steady-state free precession (bSSFP) imaging with 0.37 mm(3) voxel volume at 3.0 T. METHODS: In fMRI experiments, full and unilateral visual field 5 Hz flashing checkerboard stimulations were given to healthy subjects. The bSSFP imaging experiments were performed at three different frequency offsets to widen the coverage, with functional activations in the primary visual cortex analyzed using the general linear model. Variations of the spatial resolution were achieved by removing outer k-space data components. RESULTS: Results show that a reduction in voxel volume from 3.44 × 3.44 × 2 mm(3) to 0.43 × 0.43 × 2 mm(3) has resulted in an increase of the functional activation signals from (7.7 ± 1.7)% to (20.9 ± 2.0)% at 3.0 T, despite of the threefold SNR decreases in the original images, leading to nearly invariant functional contrast-to-noise ratios (fCNR) even at high spatial resolution. Activation signals aligning nicely with gray matter sulci at high spatial resolution would, on the other hand, have possibly been mistaken as noise at low spatial resolution. CONCLUSIONS: It is concluded that the bSSFP sequence is a plausible technique for fMRI investigations at submillimeter voxel widths without compromising fCNR. The reduction of partial volume averaging with nonactivated brain tissues to retain fCNR is uniquely suitable for high spatial resolution applications such as the resolving of columnar organization in the brain.

Sequential change in T2* values of cartilage, meniscus, and subchondral bone marrow in a rat model of knee osteoarthritis.

BACKGROUND: There is an emerging interest in using magnetic resonance imaging (MRI) T2* measurement for the evaluation of degenerative cartilage in osteoarthritis (OA). However, relatively few studies have addressed OA-related changes in adjacent knee structures. This study used MRI T2* measurement to investigate sequential changes in knee cartilage, meniscus, and subchondral bone marrow in a rat OA model induced by anterior cruciate ligament transection (ACLX). MATERIALS AND METHODS: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group). Group 1 was the normal control group. Groups 2 and 3 received ACLX and sham-ACLX, respectively, of the right knee. T2* values were measured in the knee cartilage, the meniscus, and femoral subchondral bone marrow of all rats at 0, 4, 13, and 18 weeks after surgery. RESULTS: Cartilage T2* values were significantly higher at 4, 13, and 18 weeks postoperatively in rats of the ACLX group than in rats of the control and sham groups (p<0.001). In the ACLX group (compared to the sham and control groups), T2* values increased significantly first in the posterior horn of the medial meniscus at 4 weeks (p = 0.001), then in the anterior horn of the medial meniscus at 13 weeks (p<0.001), and began to increase significantly in the femoral subchondral bone marrow at 13 weeks (p = 0.043). CONCLUSION: Quantitative MR T2* measurements of OA-related tissues are feasible. Sequential change in T2* over time in cartilage, meniscus, and subchondral bone marrow were documented. This information could be potentially useful for in vivo monitoring of disease progression.

T2 values of posterior horns of knee menisci in asymptomatic subjects.

PURPOSE: The magnetic resonance (MR) T2 value of cartilage is a reliable indicator of tissue properties and therefore may be used as an objective diagnostic tool in early meniscal degeneration. The purpose of this study was to investigate age, gender, location, and zonal differences in MR T2 value of the posterior horns of knee menisci in asymptomatic subjects. METHODS: Sixty asymptomatic volunteers (30 men and 30 women) were enrolled and divided into three different age groups: 20-34, 35-49 and 50-70 years. The inclusion criteria were BMI<30 kg/cm(2), normalized Western Ontario and McMaster Universities (WOMAC) pain score of zero, and no evidence of meniscal and ligamentous abnormalities on routine knee MR imaging. The T2 values were measured on images acquired with a T2-weighted fat-suppressed turbo spin-echo sequence at 3T. RESULTS: The mean T2 values in both medial and lateral menisci for the 20-34, 35-49, and 50-70 age groups were 9.94 msec±0.94, 10.73 msec±1.55, and 12.36 msec±2.27, respectively, for women and 9.17 msec±0.74, 9.64 msec±0.67, and 10.95 msec±1.33, respectively, for men. The T2 values were significantly higher in the 50-70 age group than the 20-34 age group (P<0.001) and in women than in men (P = 0.001, 0.004, and 0.049 for each respective age group). T2 values were significantly higher in medial menisci than in lateral menisci only in women age 50-70 (3.33 msec, P = 0.006) and in the white zone and red/white zone of the 50-70 and 35-49 age groups than that of the 20-34 age group (2.47, 1.02; 2.77, 1.16 msec, respectively, all P<0.01). CONCLUSION: The MR T2 values of the posterior meniscal horns increase with increasing age in women and are higher in women than in men. The age-related rise of T2 values appears to be more severe in medial menisci than in lateral menisci. Differences exist in the white zone and red/white zone.

Direct magnetic resonance detection of myelin and prospects for quantitative imaging of myelin density.

Magnetic resonance imaging has previously demonstrated its potential for indirectly mapping myelin density, either by relaxometric detection of myelin water or magnetization transfer. Here, we investigated whether myelin can be detected and possibly quantified directly. We identified the spectrum of myelin in the spinal cord in situ as well as in myelin lipids extracted via a sucrose gradient method, and investigated its spectral properties. High-resolution solution NMR spectroscopy showed the extract composition to be in agreement with myelin's known chemical make-up. The 400-MHz (1)H spectrum of the myelin extract, at 20 °C (room temperature) and 37 °C, consists of a narrow water resonance superimposed on a broad envelope shifted ∼3.5 ppm upfield, suggestive of long-chain methylene protons. Superimposed on this signal are narrow components resulting from functional groups matching the chemical shifts of the constituents making up myelin lipids. The spectrum could be modeled as a sum of super-Lorentzians with a T(2)* distribution covering a wide range of values (0.008-26 ms). Overall, there was a high degree of similarity between the spectral properties of extracted myelin lipids and those found in neural tissue. The normalized difference spectrum had the hallmarks of membrane proteins, not present in the myelin extract. Using 3D radially ramp-sampled proton MRI, with a combination of adiabatic inversion and echo subtraction, the feasibility of direct myelin imaging in situ is demonstrated. Last, the integrated signal from myelin suspensions is shown, both spectroscopically and by imaging, to scale with concentration, suggesting the potential for quantitative determination of myelin density.