Gender- and Age-Associated Differences in Bone Marrow Adipose Tissue and Bone Marrow Fat Unsaturation Throughout the Skeleton, Quantified Using Chemical Shift Encoding-Based Water-Fat MRI.

Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to determine region-specific variations and age- and gender-specific differences in BMAT and BMAT composition in healthy subjects. In this cross-sectional study, we included 40 healthy subjects (26 male: mean age 49 years, range 22-75 years; 14 female: mean age 50 years, range 29-71) and determined the bone marrow signal fat fraction and bone marrow unsaturation in the spine (C3-L5), pelvis, femora, and tibiae using chemical shift encoding-based water-fat imaging (WFI) with multiple gradient echoes (mGRE). Regions of interest covered the individual vertebral bodies, pelvis and proximal epimetaphysis, diaphysis, and distal epimetaphysis of the femur and tibia. The spinal fat fraction increased from cervical to lumbar vertebral bodies (mean fat fraction ( ± SD or (IQR): cervical spine 0.37 ± 0.1; thoracic spine 0.41 ± 0.08. lumbar spine 0.46 ± 0.01; p < 0.001). The femoral fat fraction increased from proximal to distal (proximal 0.78 ± 0.09; diaphysis 0.86 (0.15); distal 0.93 ± 0.02; p < 0.001), while within the tibia the fat fraction decreased from proximal to distal (proximal 0.92 ± 0.01; diaphysis 0.91 (0.02); distal 0.90 ± 0.01; p < 0.001). In female subjects, age was associated with fat fraction in the spine, pelvis, and proximal femur (ρ = 0.88 p < 0.001; ρ = 0.87 p < 0.001; ρ = 0.63 p = 0.02; ρ = 0.74 p = 0.002, respectively), while in male subjects age was only associated with spinal fat fraction (ρ = 0.40 p = 0.04). Fat fraction and unsaturation were negatively associated within the spine (r = -0.40 p = 0.01), while in the extremities fat fraction and unsaturation were positively associated (distal femur: r = 0.42 p = 0.01; proximal tibia: r = 0.47, p = 0.002; distal tibia: r = 0.35 p = 0.03), both independent of age and gender. In conclusion, we confirm the distinct, age- and gender-dependent, distribution of BMAT throughout the human skeleton and we show that, contradicting previous animal studies, bone marrow unsaturation in human subjects is highest within the axial skeleton compared to the appendicular skeleton. Furthermore, we show that BMAT unsaturation was negatively correlated with BMAT within the spine, while in the appendicular skeleton, BMAT and BMAT unsaturation were positively associated.

Changes in sub-calcaneal fat pad composition and their association with dynamic plantar foot pressure in people with diabetic neuropathy.

BACKGROUND: Diabetic foot disease is associated with physiological and biomechanical abnormalities in the foot that increase risk for ulceration. The objective was to assess MRI changes in the composition of sub-calcaneal fat pad tissue and its association with plantar pressure during walking. METHODS: Fourteen people with diabetes and peripheral neuropathy and five age-matched healthy controls underwent T1-weighted sagittal plane spin-echo Dixon MRI of the rearfoot. Dixon Chemical Shift Imaging was used to create fat-only and water-only images from which the fat signal fraction in a defined ROI of the sub-calcaneal fat pad was calculated. Barefoot plantar pressure distribution during walking was assessed and associated with fat pad outcomes. FINDINGS: Mean ± SD fat signal fraction was significantly lower in the neuropathic subjects than in the healthy controls (0.55 ± 0.11 vs. 0.72 ± 0.03, p < 0.005), and was explained by a lowering in fat signal (R2 0.87), more than an increase in water signal (R2 0.32). Mean ± SD peak pressure at the heel was 391 ± 119 kPa for the neuropathic subjects and 325 ± 53 kPa for the healthy controls (non-significantly different). Fat signal fraction and peak pressure were significantly inversely correlated (r = -0.59, p < 0.01). INTERPRETATION: Dixon chemical shift MRI showed a reduced fat signal fraction in sub-calcaneal fat pad tissue in people with diabetic neuropathy. Both neuropathic and non-neuropathic factors may be attributed to this outcome. Fat pad function also seems to be compromised, as indicated by an associated increase in peak plantar pressures. This may increase risk for foot ulceration.

The Effect of Roux-en-Y Gastric Bypass on Bone Marrow Adipose Tissue and Bone Mineral Density in Postmenopausal, Nondiabetic Women.

OBJECTIVES: This study aimed to determine the effect of bariatric surgery-induced weight loss on bone marrow adipose tissue (BMAT) and bone mineral density (BMD) in postmenopausal, nondiabetic women. METHODS: A total of 14 postmenopausal, nondiabetic women with obesity who were scheduled for laparoscopic Roux-en-Y gastric bypass surgery (RYGB) were included in this study. Vertebral bone marrow fat signal fraction was determined by quantitative chemical shift magnetic resonance imaging, and vertebral volumetric BMD (vBMD) was determined by quantitative computed tomography before surgery and 3 and 12 months after surgery. Data were analyzed by linear mixed model. RESULTS: Body weight [mean (SD)] decreased after surgery from 108 (13) kg at baseline to 89 (12) kg at 3 months and 74 (11) kg at 12 months (P < 0.001). BMAT decreased after surgery from 51% (8%) at baseline to 50% (8%) at 3 months and 46% (7%) at 12 months (P = 0.004). vBMD decreased after surgery from 101 (26) mg/cm3 at baseline to 94 (28) mg/cm3 at 3 months (P = 0.003) and 94 (28) mg/cm3 at 12 months (P = 0.035). Changes in BMAT and vBMD were not correlated (ρ = -0.10 and P = 0.75). Calcium and vitamin D concentrations did not change after surgery. CONCLUSIONS: RYGB decreases both BMAT (after 12 months) and vBMD (both after 3 months and 12 months) in postmenopausal, nondiabetic women. Changes in BMAT and vBMD were not correlated. These findings suggest that BMAT does not contribute to bone loss following RYGB.

Iron storage in liver, bone marrow and splenic Gaucheroma reflects residual disease in type 1 Gaucher disease patients on treatment.

Gaucher disease (GD) is a lysosomal storage disorder characterized by the storage of glycosphingolipids in macrophages. Despite effective therapy, residual disease is present in varying degrees and may be associated with late complications, such as persistent bone or liver disease and increased cancer risk. Gaucher macrophages are capable of storing iron and locations of residual disease may thus be detectable with iron imaging. Forty type 1 GD (GD1) patients and 40 matched healthy controls were examined using a whole-body magnetic resonance imaging protocol consisting of standard sequences, allowing analysis of iron content per organ, expressed as R2* (Hz). Median R2* values were significantly elevated in GD1 patients as compared to healthy controls in liver [41 Hz (range 29-165) vs. 38 Hz (range 28-53), P < 0·01], femoral bone marrow [54 Hz (range 37-129) vs. 49 Hz (range 39-69), P = 0·036] and vertebral bone marrow (118 Hz (range 82-210) vs. 105 Hz (range 76-149), P < 0·01). In the spleen, primarily focal Gaucher lesions known as Gaucheroma were found to have increased R2* values. R2* values of liver, spleen and vertebral bone marrow strongly correlated with serum ferritin levels. GD1 patients with persistent hyperferritinaemia demonstrate increased iron levels in liver and bone marrow, which may carry a risk for liver fibrosis and cancer.

Comparison of clinical MRI liver iron content measurements using signal intensity ratios, R 2 and R 2.

PURPOSE: To compare three types of MRI liver iron content (LIC) measurement performed in daily clinical routine in a single center over a 6-year period. METHODS: Patients undergoing LIC MRI-scans (1.5T) at our center between January 1, 2008 and December 31, 2013 were retrospectively included. LIC was measured routinely with signal intensity ratio (SIR) and MR-relaxometry (R 2 and R 2*) methods. Three observers placed regions-of-interest. The success rate was the number of correctly acquired scans over the total number of scans. Interobserver agreement was assessed with intraclass correlation coefficients (ICC) and Bland-Altman analysis, correlations between LICSIR, R 2, R 2*, and serum values with Spearman's rank correlation coefficient. Diagnostic accuracies of LICSIR, R 2 and serum transferrin, transferrin-saturation, and ferritin compared to increased R 2* (≥44 Hz) as indicator of iron overload were assessed using ROC-analysis. RESULTS: LIC MRI-scans were performed in 114 subjects. SIR, R 2, and R 2* data were successfully acquired in 102/114 (89%), 71/114 (62%), and 112/114 (98%) measurements, with the lowest success rate for R 2. The ICCs of SIR, R 2, and R 2* did not differ at 0.998, 0.997, and 0.999. R 2 and serum ferritin had the highest diagnostic accuracies to detect elevated R 2* as mark of iron overload. CONCLUSIONS: SIR and R 2* are preferable over R 2 in terms of success rates. R 2*'s shorter acquisition time and wide range of measurable LIC values favor R 2* over SIR for MRI-based LIC measurement.

Short-Term Effect of Estrogen on Human Bone Marrow Fat.

Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p = 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, -0.01 to 0.04) during the luteal phase (p = 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17-ß estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17-ß estradiol administration (p < 0.001) and increased again after cessation. During 17-ß estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p = 0.034) and the bone resorption marker C-terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17-ß estradiol rapidly reduces the marrow fat fraction, suggesting that 17-ß estradiol regulates bone marrow fat independent of bone mass.

Liver fibrosis in type I Gaucher disease: magnetic resonance imaging, transient elastography and parameters of iron storage.

Long term liver-related complications of type-1 Gaucher disease (GD), a lysosomal storage disorder, include fibrosis and an increased incidence of hepatocellular carcinoma. Splenectomy has been implicated as a risk factor for the development of liver pathology in GD. High ferritin concentrations are a feature of GD and iron storage in Gaucher cells has been described, but iron storage in the liver in relation to liver fibrosis has not been studied. Alternatively, iron storage in GD may be the result of iron supplementation therapy or regular blood transfusions in patients with severe cytopenia. In this pilot study, comprising 14 type-1 GD patients (7 splenectomized, 7 non-splenectomized) and 7 healthy controls, we demonstrate that liver stiffness values, measured by Transient Elastography and MR-Elastography, are significantly higher in splenectomized GD patients when compared with non-splenectomized GD patients (p = 0.03 and p = 0.01, respectively). Liver iron concentration was elevated (>60±30 µmol/g) in 4 GD patients of whom 3 were splenectomized. No relationship was found between liver stiffness and liver iron concentration. HFE gene mutations were more frequent in splenectomized (6/7) than in non-splenectomized (2/7) participants (p = 0.10). Liver disease appeared more advanced in splenectomized than in non-splenectomized patients. We hypothesize a relationship with excessive hepatic iron accumulation in splenectomized patients. We recommend that all splenectomized patients, especially those with evidence of substantial liver fibrosis undergo regular screening for HCC, according to current guidelines.

Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes.

This paper describes the effects of a switch to velaglucerase alfa in a group of adult patients with type 1 Gaucher disease, all of whom had previously had their dose reduced as a consequence of the worldwide imiglucerase shortage. Thirty-two patients from two large European Gaucher centers switched to treatment with velaglucerase alfa after 1-8.5 months of dose reduction. The course of important Gaucher disease parameters was studied at four time points: one year before the shortage, just before the shortage, before a switch to velaglucerase and after up to one year of treatment with velaglucerase. These parameters included hemoglobin concentration, platelet count, plasma chitotriosidase activity in all patients, and spleen and liver volumes (as well as bone marrow fat fraction images) in 10 patients. Decreases in platelet counts as a result of reduced treatment with imiglucerase were quickly restored on treatment with velaglucerase alfa. Chitotriosidase activity declined overall after switching. Five out of 10 patients had an increase in liver volume of at least 10% after six months of velaglucerase treatment, which was reversible in 3. Most patients received infusions at home and no important side effects were observed. Velaglucerase alfa appears to be a safe and effective alternative for imiglucerase.

From Gaucher's disease to metabolic radiology: translational radiological research and clinical practice.

Imaging has an increasing role in the management of patients with inborn errors of metabolism. This role is related to expensive enzyme replacement therapy that requires a surrogate biomarker, such as magnetic resonance imaging. This review paper raises the issue of the potential for metabolic radiology to become a subspecialty.

MRI for staging lymphoma: whole-body or less?

PURPOSE: To assess whether whole-body MRI detects more clinically relevant lesions (i.e., leading to a change in Ann Arbor stage) than an MRI protocol that only includes the head/neck and trunk (i.e., from cranial vertex to groin, excluding the arms) in patients with lymphoma. MATERIALS AND METHODS: One hundred consecutive patients with newly diagnosed lymphoma prospectively underwent T1-weighted and T2-weighted short inversion time inversion recovery whole-body MRI. The number of lymphomatous sites at MRI with a field of view (FOV) limited to the head/neck and trunk, and the additional number of lymphomatous sites at whole-body MRI and their influence on Ann Arbor stage were determined. RESULTS: At MRI with a FOV limited to the head/neck and trunk, 507 sites were classified as lymphomatous. At whole-body MRI, 7 additional sites outside the head/neck and trunk in 7 patients (7.0%; 95% confidence interval: 3.4-13.8%) were classified as lymphomatous, but Ann Arbor stage never changed. CONCLUSION: Whole-body MRI did not detect any clinically relevant lesions outside the FOV of an MRI protocol that only includes the head/neck and trunk. Therefore, it may be sufficient to only include the head/neck and trunk when using MRI for staging lymphoma.

Upper and extra-motoneuron involvement in early motoneuron disease: a diffusion tensor imaging study.

Motoneuron disease is a term encompassing three phenotypes defined largely by the balance of upper versus lower motoneuron involvement, namely amyotrophic lateral sclerosis, primary lateral sclerosis and progressive muscular atrophy. However, neuroradiological and pathological findings in these phenotypes suggest that degeneration may exceed the neuronal system upon which clinical diagnosis is based. To further delineate the phenotypes within the motoneuron disease spectrum, this controlled study assessed the upper- and extra-motoneuron white matter involvement in cohorts of patients with motoneuron disease phenotypes shortly after diagnosis by comparing diffusion tensor imaging data of the different cohorts to those of healthy controls and directly between the motoneuron disease phenotypes (n = 12 for each cohort). Furthermore, we acquired follow-up data 6 months later to evaluate fractional anisotropy changes over time. Combined use of diffusion tensor tractography of the corticospinal tract and whole-brain voxel-based analysis allowed for comparison of the sensitivity of these techniques to detect white matter involvement in motoneuron disease. The voxel-based analysis demonstrated varying extents of white matter involvement in different phenotypes of motoneuron disease, albeit in quite similar anatomical locations. In general, fractional anisotropy reductions were modest in progressive muscular atrophy and most extensive in primary lateral sclerosis. The most extensive patterns of fractional anisotropy reduction were observed over time in the voxel-based analysis, indicating progressive extra-motor white matter degeneration in limb- and bulbar onset amyotrophic lateral sclerosis and in progressive muscular atrophy. The observation of both upper motor and extra-motoneuron involvement in all phenotypes of motoneuron disease shortly after diagnosis suggests that these are all part of a single spectrum of multisystem neurodegenerative disease. Voxel-based analysis was more sensitive to detect longitudinal changes than diffusion tensor tractography of the corticospinal tract. Voxel-based analyses may be particularly valuable in the evaluation of motor and extra-motor white matter involvement in the early symptomatic stages of motoneuron disease, and for monitoring the spread of pathology over time.

The direct tensor solution and higher-order acquisition schemes for generalized diffusion tensor imaging.

Both in diffusion tensor imaging (DTI) and in generalized diffusion tensor imaging (GDTI) the relation between the diffusion tensor and the measured apparent diffusion coefficients is given by a tensorial equation, which needs to be inverted in order to solve the diffusion tensor. The traditional way to do this does not preserve the tensorial structure of the equation, which we consider a weakness in the method. For a physically correct measurement procedure, the condition number of the acquisition scheme, which is a determinant of the noise behavior, needs to be rotationally invariant. The method which traditionally is used to find such schemes, however, is cumbersome and mathematically unsatisfactory. This is considered a second weakness, closely connected to the first. In this paper we present an alternative inversion of the diffusion tensor equation, which does preserve the tensor form, for arbitrary order, and which is named the direct tensor solution (DTS). The DTS is derived under the assumption that the apparent diffusion coefficient in any direction is known, i.e. in the infinite acquisition scheme. Whenever the DTS is valid for a given finite acquisition scheme and for a given order, the condition number is rotationally invariant. The DTS provides a compact, algebraic procedure to check this rotational invariance. We also present a method to construct acquisition schemes, for which the DTS is valid for the measurement of higher-order diffusion tensors. Furthermore, the DTS leads to other mathematical insights, such as tensorial relationships between diffusion tensors of different orders, and a more general understanding of the Platonic Variance Method, which we published before.

White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis.

There is increasing evidence of white matter pathology in schizophrenia. The aim of this study was to examine whether white matter abnormalities found with diffusion tensor imaging (DTI) in previous schizophrenia studies are present in the early phase of the illness. DTI was performed at 3 T on 10 male patients with a first (n = 8) or second (n = 2) psychotic episode of schizophrenia or schizoaffective disorder, 10 male patients at ultra-high risk of psychosis with (pre)psychotic symptoms and 10 healthy controls. Fibertracts found to be abnormal in other DTI studies (uncinate and arcuate fasciculus, anterior and dorsal cingulum, subdivisions of the corpus callosum) were calculated and visualized; tract-specific measurements (fractional anisotropy and trace) were performed. No differences were found between the healthy subjects and the 2 patient groups. These preliminary findings suggest that there is no white matter pathology of these association tracts detectable with DTI in the early stages of schizophrenic illness in males. Our findings are in contrast with DTI abnormalities found in some other first-episode studies. This discrepancy in findings may be related to differences in subject characteristics and DTI methodology. Possible effects of age, gender, level of education and illicit substance use on DTI findings in schizophrenia are discussed.

Generating fiber crossing phantoms out of experimental DWIs.

In Diffusion Tensor Imaging (DTI), differently oriented fiber bundles inside one voxel are incorrectly modeled by a single tensor. High Angular Resolution Diffusion Imaging (HARDI) aims at using more complex models, such as a two-tensor model, for estimating two fiber bundles. We propose a new method for creating experimental phantom data of fiber crossings, by mixing the DWI-signals from high FA-regions with different orientation. The properties of these experimental phantoms approach the conditions of real data. These phantoms can thus serve as a 'ground truth' in validating crossing reconstruction algorithms. The angular resolution of a dual tensor model is determined using series of crossings, generated under different angles. An angular resolution of 0.67pi was found in data scanned with a diffusion weighting parameter b = 1000 s/mm2. This resolution did not change significantly in experiments with b = 3000 and 5000 s/mm2, keeping the scanning time constant.

Low frequency maintenance therapy with imiglucerase in adult type I Gaucher disease: a prospective randomized controlled trial.

BACKGROUND AND OBJECTIVES: Gaucher disease type I can be successfully treated with enzyme replacement therapy (ERT). In order to reduce the burden of the intravenously administered enzyme, a low frequency of administration was prospectively studied in patients with stable and minor disease following ERT. DESIGN AND METHODS: Eleven patients were randomly assigned either to continue their original regimen of a dose of ERT once every week or fortnight (five patients) or to lower the frequency of administration to once every 4 weeks, at the same cumulative dose (six patients). The primary end-point was change in liver ratio (mL/kg body weight). Secondary end-points were spleen volume, hemoglobin level, platelet count, lumbar bone marrow fat content measured with quantitative chemical shift imaging (QCSI), white cell count, and plasma levels of ferritin, chitotriosidase, liver enzymes and angiotensin-converting enzyme (ACE). RESULTS: There were no significant mean differences between the two treatment arms in liver ratio or any of the other end-points. However, there were two treatment failures in the low frequency of administration group. These patients showed progression of disease as evidenced by a reduction of QCSI in one patient and an increase in liver ratio as well as a slow decrease in QCSI in the other. Both patients already had relatively low baseline QCSI values. One patient switched back to the original regimen at 6 months because of subjective complaints. INTERPRETATION AND CONCLUSIONS: Low frequency ERT in adult Gaucher type I patients maintains stable disease in most, but not all patients with stable and minimal disease. Close monitoring of all disease parameters remains mandatory.

Dynamic contrast-enhanced MRI of the bowel wall for assessment of disease activity in Crohn's disease.

OBJECTIVE: The purpose of this study was to evaluate the role of contrast-enhanced dynamic MRI in predicting the disease activity of Crohn's disease. MATERIALS AND METHODS: Forty-eight patients in two hospitals who had clinically suspected exacerbation of Crohn's disease were included in this study. In three levels of thickened small-bowel wall, axial dynamic T1-weighted sequences were performed every 4-6 sec for a total duration of 2-3 min after contrast administration; static T1-weighted turbo spin-echo sequences were acquired both before and after contrast administration. The slope of enhancement, enhancement ratio, time to enhancement, enhancement time, and thickness of the small-bowel wall were determined. These MRI results were compared with overall clinical grade, Crohn's disease activity index (CDAI), and Van Hees activity index. Clinical grade was based on clinical information, physical findings, laboratory studies, endoscopy, surgery, and other imaging studies. Spearman's correlation coefficient and p values were determined per hospital. Fisher's z-transformation was applied before pooling the correlation coefficients from both hospitals. RESULTS: The enhancement ratio based on the static series showed significant correlation with the clinical grade (r = 0.29, p = 0.045), CDAI (r =0.31, p = 0.033), and Van Hees activity index (r = 0.36, p = 0.016). The enhancement ratio based on the dynamic series correlated significantly with the CDAI (r = 0.38, p = 0.016). Wall thickness correlated significantly with clinical grade (r = 0.47, p = 0.003) and Van Hees activity index (r = 0.41, p = 0.007). CONCLUSION: These data suggest that the enhancement ratio of bowel wall after IV administration of gadodiamide and bowel wall thickness are weak to moderate indicators of the severity of Crohn's disease.

Tilt table design for rapid and sinusoidal posture change with minimal vestibular stimulation.

INTRODUCTION: Cardiovascular response to fast posture change can be used to model individual orthostatic response under normal circumstances and after spaceflight. We set out to construct a computer-controlled tilt table suitable for repeated sinusoidal tilt motion as well as fast, single head-up tilt (HUT). The movement profile of the table was designed to prevent muscle tensing and limit vestibular stimulation. METHODS: On the new table, 20 healthy subjects underwent a protocol of fast HUT and sinusoidal tilt motion at 2.5 tilts per minute. BP was measured non-invasively (Finapres). Time domain dynamic response to HUT and frequency domain response to sinusoidal tilts were derived from the beat-to-beat BP and from interbeat-interval (IBI) series. RESULTS: Tilt motion did not induce dizziness and was experienced by all subjects as smooth. The systolic BP response to fast HUT correlated mildly with the systolic BP spectral power at the sinusoidal tilt frequency (R = 0.47). The IBI response to fast HUT correlated well with the IBI power at the sinusoidal tilt frequency (R = 0.74). DISCUSSION: In this study we presented a computer controlled tilt table capable of fast posture change and sinusoidal tilts. An exploratory protocol demonstrated that the table is suitable for obtaining cardiovascular response to posture change for modeling purposes.

Peroxisomal biogenesis disorder: comparison of conventional MR imaging with diffusion-weighted and diffusion-tensor imaging findings.

BACKGROUND AND PURPOSE: Peroxisomal biogenesis disorders (PBDs) refer to a group of disorders of peroxisomal biogenesis causing neuronal migration disorder, delayed myelination, and demyelination. The aim of this study was to evaluate the added value of diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) compared with that of conventional T2-weighted imaging in assessing the extent of white matter damage in patients with PBDs. METHODS: Three patients (aged 12, 16, and 80 months) with PBD (type 1 protein targeting sequence [PTS1]) and three age-matched control subjects underwent MR imaging on a 1.5-T system. The protocol included axial T2-weighted, DWI, and DTI sequences. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) changes were calculated using regions of interest at several predefined white matter areas and compared with those of age-matched control subjects. Color-coded maps were obtained to visualize the range of FA values. RESULTS: On the T2-weighted images, one patient revealed severe hypomyelination throughout the brain; the two other patients showed focal abnormal high-signal-intensity areas. All patients had significantly decreased FA values in white matter areas that appeared abnormal on the T2-weighted images. In two of the three patients, significant FA reduction was also found in normal-appearing white matter. The ADC values of the patients were significantly increased compared with those of the age-matched controls. CONCLUSION: Although based on a small number of patients, our data suggest that DWI and DTI can be used to characterize and quantify white matter tract injury in patients with PBD-PTS1. Furthermore, our data suggest that these techniques have the potential to identify neurodegenerative changes not yet visible on T2-weighted images.

Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings.

Conventional MR, diffusion-weighted, and diffusion tensor imaging were performed in an 8-day-old girl with citrullinemia. She had severe hyperammonemia for several days. On conventional T2-weighted MR images, symmetric, confluent high signal intensity was found in the bilateral thalami, basal ganglia, cortex, and subcortical white matter. Diffusion-weighted imaging demonstrated decreased apparent diffusion coefficient in these areas, reflecting cytotoxic edema. Follow-up MR imaging at the age of 4 months revealed subcortical cysts, ulegyric changes, and atrophy, which were most prominent in the occipital lobes. Diffusion tensor imaging revealed decreased anisotropy throughout the brain, consistent with diffuse injury to the oligodendro-axonal unit. Diffusion-weighted and diffusion tensor imaging are valuable techniques for the detection of irreversible brain damage and for the characterization of hyperintense lesions on T2-weighted MR images in patients with the neonatal form of citrullinemia.

Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to Dixon quantitative chemical shift MR imaging--initial experience.

PURPOSE: To develop a semiquantitative magnetic resonance (MR) imaging bone marrow burden (BMB) score with inclusion of both axial and peripheral bone marrow in Gaucher disease as an alternative to MR imaging with the Dixon quantitative chemical shift imaging (QCSI) technique. MATERIALS AND METHODS: Two experienced musculoskeletal radiologists with no experience in evaluating Gaucher disease blindly analyzed MR images of lumbar spines and femora. Interobserver and intraobserver variability were tested. In addition, the BMB score was determined as a parameter to evaluate bone marrow response to enzyme supplementation therapy. Finally, the BMB score was compared with fat fraction measurements obtained with Dixon QCSI. Differences between groups were analyzed by using the nonparametric Mann-Whitney test. A P value of less than.05 was considered to represent significance. Correlation was calculated by using two-tailed nonparametric rank correlation (Spearman rho). RESULTS: In 30 patients (mean age, 39.3 years; age range, 12-71 years) the mean fat fraction was 0.20 (range, 0.08-0.40). The BMB score range was 3-13 points. A significant correlation was found between the two observers when using BMB (rho = 0.91, P <.001). The intraobserver variation showed a significant correlation (rho = 0.99, P <.001). There was a significant correlation between BMB and QCSI (rho = -0.78, P <.001). Although BMB was less sensitive than Dixon QCSI, it showed enough sensitivity to allow detection of bone marrow response to enzyme supplementation therapy. CONCLUSION: BMB is a reproducible semiquantitative scoring system that is easy to use. It combines MR imaging of both axial and peripheral bone marrow and shows a significant correlation with QCSI.