A cross-sectional natural history study of aspartylglucosaminuria.

Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder that causes stagnation of development in adolescence and neurodegeneration in early adulthood. Precision therapies, including gene transfer therapy, are in development with a goal of taking advantage of the slow clinical course. Understanding of disease natural history and identification of disease-relevant biomarkers are important steps in clinical trial readiness. We describe the clinical features of a diverse population of patients with AGU, including potential imaging and electrophysiological biomarkers. This is a single-center, cross-sectional study of the clinical, neuropsychological, electrophysiological, and imaging characteristics of AGU. A comprehensive assessment of eight participants (5 Non-Finnish) revealed a mean non-verbal IQ (NVIQ) of 70.25 ± 10.33 which decreased with age (rs = -0.85, p = 0.008). All participants demonstrated deficits in communication and gross/fine motor dysfunction. Auditory and visual evoked potentials demonstrated abnormalities in one or both modalities in 7 of 8 subjects, suggesting sensory pathway dysfunction. Brain imaging demonstrated T2 FLAIR hypointensity in the pulvinar nuclei and cerebral atrophy, as previously shown in the Finnish AGU population. Magnetic resonance spectroscopy (MRS) showed a 5.1 ppm peak corresponding to the toxic substrate (GlcNAc-Asn), which accumulates in AGU. Our results showed there was no significant difference between Finnish and Non-Finnish patients, and performance on standardized cognitive and motor testing was similar to prior studies. Age-related changes on functional assessments and disease-relevant abnormalities on surrogate biomarkers, such as MRS, could be used as outcome measures in a clinical trial.

Anterior Pituitary Volume in Patients with Transfusion Dependent Anemias: Volumetric Approaches and Relation to Pituitary MRI­R2.

PURPOSE: Anterior pituitary iron overload and volume shrinkage is common in patients with transfusion-dependent anemia and associated with growth retardation and hypogonadotropic hypogonadism. We investigated the accuracy of different MRI-based pituitary volumetric approaches and the relationship between pituitary volume and MRI-R2, particularly with respect to growth and hypogonadism. METHODS: In 43 patients with transfusion-dependent anemia (12-38 years) and 32 healthy controls (12-72 years), anterior pituitary volume was measured by a sagittal T1 GRE 3D sequence at 1.5T and analyzed by 3D semi-automated threshold volumetry (3D-volumetry). This reference method was compared with planimetric 2D-volumetry, approximate volume calculations, and pituitary height. Using a multiple SE sequence, pituitary iron as MRI-R2 was assessed by fitting proton signal intensities to echo times. Growth and hypogonadism were obtained from height percentile tables and patients' medical charts. From body surface area and age adjusted anterior pituitary volumes of controls, Z­scores were calculated for all subjects. Separation of controls and patients with respect to Z and pituitary R2 was performed by bivariate linear discriminant analysis. RESULTS: Tuned 2D volumes showed highest agreement with reference 3D-volumes (bias -4.8%; 95% CI:-8.8%|-0.7%). A linear discriminant equation of Z = -17.8 + 1.45 · R2 revealed optimum threshold sensitivity and specificity of 65% and 100% for discrimination of patients from controls, respectively. Of correctly classified patients 71% and 75% showed hypogonadism and growth retardation, respectively. CONCLUSION: Accurate assessment of anterior pituitary size requires 3D or precise 2D volumetry, with shorter analysis time for the latter. Anterior pituitary volume Z­scores and R2 allow for the identification of patients at risk of pituitary dysfunction.

Probing an AI regression model for hand bone age determination using gradient-based saliency mapping.

Understanding how a neural network makes decisions holds significant value for users. For this reason, gradient-based saliency mapping was tested on an artificial intelligence (AI) regression model for determining hand bone age from X-ray radiographs. The partial derivative (PD) of the inferred age with respect to input image intensity at each pixel served as a saliency marker to find sensitive areas contributing to the outcome. The mean of the absolute PD values was calculated for five anatomical regions of interest, and one hundred test images were evaluated with this procedure. The PD maps suggested that the AI model employed a holistic approach in determining hand bone age, with the wrist area being the most important at early ages. However, this importance decreased with increasing age. The middle section of the metacarpal bones was the least important area for bone age determination. The muscular region between the first and second metacarpal bones also exhibited high PD values but contained no bone age information, suggesting a region of vulnerability in age determination. An end-to-end gradient-based saliency map can be obtained from a black box regression AI model and provide insight into how the model makes decisions.

Measurement and evaluation of specific absorption rate and temperature elevation caused by an artificial hip joint during MRI scanning.

A primary safety concern in a magnetic resonance imaging environment is heating of metallic implants by absorbing radiofrequency (RF) energy during MRI scanning. Experimental measurement in conjunction with computational modeling was used to evaluate the risk of biological tissue injury from the RF heating of artificial hip joints by obtaining both specific absorption rate (SAR) and temperature elevation at 1.5 T and 3 T MRI systems. Simulation result showed that high SAR and high temperature appeared near both head and tail sections of the artificial hip joints. For five different 1.5 T and 3 T MRI systems, measured temperature location showed that high temperature rises occurred near both head and tail regions of the metallic hip joints. Measured SAR value of 24.6 W/kg and the high temperature rise (= 4.22 °C) occurred in the tail region of the hip joint at 1.5 T, which was higher than the limits for temperature required by the international electrotechnical commission 60601-2-33. We have demonstrated the feasibility of evaluating RF heating of metallic hip joints during MRI scans.

Pituitary iron and factors predictive of fertility status in transfusion dependent thalassemia.

Not available.

Reduction of bias in the evaluation of fractional anisotropy and mean diffusivity in magnetic resonance diffusion tensor imaging using region-of-interest methodology.

Accurate quantification of fractional anisotropy (FA) and mean diffusivity (MD) in MR diffusion tensor imaging (DTI) requires adequate signal-to-noise ratio (SNR) especially in low FA areas of the brain, which necessitates clinically impractical long image acquisition times. We explored a SNR enhancement strategy using region-of-interest (ROI)-based diffusion tensor for quantification. DTI scans from a healthy male were acquired 15 times and combined into sets with different number of signal averages (NSA = 1-4, 15) at one 1.5-T Philips and three 3-T (Philips, Siemens and GE) scanners. Equivalence test was performed to determine NSA thresholds for bias-free FA and MD quantifications by comparison with reference values derived from images with NSA = 15. We examined brain areas with low FA values including caudate nucleus, globus pallidus, putamen, superior temporal gyrus, and substructures within thalamus (lateral dorsal, ventral anterior and posterior nuclei), where bias-free FA is difficult to obtain using a conventional approach. Our results showed that bias-free FA can be obtained with NSA = 2 or 3 in some cases using ROI-based analysis. ROI-based analysis allows reliable FA and MD quantifications in various brain structures previously difficult to study with clinically feasible data acquisition schemes.

Signal-to-noise ratio assessment of muscle diffusion tensor imaging using single image set and validation by the difference image method.

OBJECTIVE: Signal-to-noise ratio (SNR) assessment is essential for accurate quantification of diffusion tensor imaging (DTI) metrics and usually requires the use of a difference image method using duplicate images. We aimed to estimate the SNR of DTI of thigh muscles using a single image set without duplicate images. METHODS: DTI of one thigh were acquired on a 3 T scanner from 15 healthy adults, and scans with number of signal averages (NSA) = 4 and 8 were repeatedly acquired. SNR were evaluated for six thigh muscles. For SNR calculation from a single image set, diffusion-weighted images with similar diffusion encoding directions were grouped into pairs. The difference image of each pair was high-pass filtered in k-space to yield noise images. Noise images were also calculated with a difference method using two image sets as a reference. Subjects were divided into two groups for filter optimization and validation, respectively. The coefficient of repeatability (CR) of the SNR obtained from the two methods was also evaluated separately. RESULTS: Bland-Altman analysis comparing the single image set method and the reference showed 95% limits of agreement of -9.2 to 9.2% for the optimization group and -12.5 to 12.6% for the validation group. The SNR measurement had a CR of 21.1% using the reference method, and 13.8% using the single image set method. CONCLUSION: The single image method can be used for DTI SNR assessment and offers better repeatability. ADVANCES IN KNOWLEDGE: SNR of skeletal muscle DTI can be assessed for any data set without duplicate images.

Obesity-Related Metabolic Risk in Sedentary Hispanic Adolescent Girls with Normal BMI.

Hispanic adolescent girls with normal BMI frequently have high body fat %. Without knowledge of body fat content and distribution, their risk for metabolic complications is unknown. We measured metabolic risk indicators and abdominal fat distribution in post-pubertal Hispanic adolescent girls with Normal BMI (N-BMI: BMI < 85th percentile) and compared these indicators between girls with Normal BMI and High Fat content (N-BMI-HF: body fat ≥ 27%; n = 15) and Normal BMI and Normal Fat content (N-BMI-NF: body fat < 27%; n = 8). Plasma concentrations of glucose, insulin, adiponectin, leptin and Hs-CRP were determined. Insulin resistance was calculated using an oral glucose tolerance test. Body fat % was measured by DXA and subcutaneous, visceral and hepatic fat by MRI/MRS. The N-BMI-HF girls had increased abdominal and hepatic fat content and increased insulin resistance, plasma leptin and Hs-CRP concentrations (p < 0.05) as compared to their N-BMI-NF counterparts. In N-BMI girls, insulin resistance, plasma insulin and leptin correlated with BMI and body fat % (p < 0.05). This research confirms the necessity of the development of BMI and body fat % cut-off criteria per sex, age and racial/ethnic group based on metabolic risk factors to optimize the effectiveness of metabolic risk screening procedures.

Improvement of Reliability of Diffusion Tensor Metrics in Thigh Skeletal Muscles.

OBJECTIVE: Quantitative diffusion tensor imaging (DTI) of skeletal muscles is challenging due to the bias in DTI metrics, such as fractional anisotropy (FA) and mean diffusivity (MD), related to insufficient signal-to-noise ratio (SNR). This study compares the bias of DTI metrics in skeletal muscles via pixel-based and region-of-interest (ROI)-based analysis. METHODS: DTI of the thigh muscles was conducted on a 3.0-T system in N = 11 volunteers using a fat-suppressed single-shot spin-echo echo planar imaging (SS SE-EPI) sequence with eight repetitions (number of signal averages (NSA) = 4 or 8 for each repeat). The SNR was calculated for different NSAs and estimated for the composite images combining all data (effective NSA = 48) as standard reference. The bias of MD and FA derived by pixel-based and ROI-based quantification were compared at different NSAs. An "intra-ROI diffusion direction dispersion angle (IRDDDA)" was calculated to assess the uniformity of diffusion within the ROI. RESULTS: Using our standard reference image with NSA = 48, the ROI-based and pixel-based measurements agreed for FA and MD. Larger disagreements were observed for the pixel-based quantification at NSA = 4. MD was less sensitive than FA to the noise level. The IRDDDA decreased with higher NSA. At NSA = 4, ROI-based FA showed a lower average bias (0.9% vs. 37.4%) and narrower 95% limits of agreement compared to the pixel-based method. CONCLUSION: The ROI-based estimation of FA is less prone to bias than the pixel-based estimations when SNR is low. The IRDDDA can be applied as a quantitative quality measure to assess reliability of ROI-based DTI metrics.

Correcting B0 Field Distortions in MRI Caused by Stainless Steel Orthodontic Appliances at 1.5 T Using Permanent Magnets - A Head Phantom Study.

Susceptibility artifacts caused by stainless steel orthodontic appliances (braces) pose significant challenges in clinical brain MRI examinations. We introduced field correction device (FCD) utilizing permanent magnets to cancel the induced B0 inhomogeneity and mitigate geometric distortions in MRI. We evaluated a prototype FCD using a 3D-printed head phantom in this proof of concept study. The phantom was compartmented into anterior frontal lobe, temporal lobe, fronto-parieto-occipital lobe, basal ganglia and thalami, brain stem, and cerebellum and had built-in orthogonal gridlines to facilitate the quantification of geometric distortions and volume obliterations. Stainless steel braces were mounted on dental models of three different sizes with total induced magnetic moment 0.15 to 0.17 A·m2. With braces B0 standard deviation (SD) ranged from 2.8 to 3.7 ppm in the temporal and anterior frontal lobes vs. 0.2 to 0.3 ppm without braces. The volume of brain regions in diffusion weighted imaging was obliterated by 32-38% with braces vs. 0% without braces in the cerebellum. With the FCD the SD of B0 ranged from 0.3 to 1.2 ppm, and obliterated volume ranged from 0 to 6% in the corresponding brain areas. These results showed that FCD can effectively decrease susceptibility artifacts from orthodontic appliances.

Feasibility of peripheral nerve MR neurography using diffusion tensor imaging adapted to skeletal muscle disease.

Background Diffusion tensor imaging (DTI) of peripheral nerves may provide additional information about nerve involvement in muscular disorders, but is considered difficult due to different optimal scan parameters tailored to magnetic resonance (MR) signal properties of muscle and neural tissues. Purpose To assess the feasibility of sciatic nerve DTI using two different approaches of region of interest (ROI)-localization in DTI scans with b-values 500 s/mm2, in participants with muscular disorders and in controls. Material and Methods DTI of the thigh was conducted on a 3T system in ten patients (6 men, 4 women; mean age =54 ± 15 years) with neuromuscular disorders and ten controls. T1-weighted (T1W) images were co-registered to fractional anisotropy (FA) color-encoded images. The apparent diffusion coefficient (ADC), FA, and fiber track length (FTL) were analyzed by two operators using a freehand ROI and a single-point ROI covering the sciatic nerve. Interclass correlation coefficient (ICC) and Bland-Altman analysis were used for evaluation of inter-operator and inter-technical agreement, respectively. Results Three-dimensional visualization of sciatic nerve fiber was achievable using both techniques. The ICC of DTI metrics showed excellent inter-operator agreement both in patients and controls. Bland-Altman analysis revealed good agreement of both techniques. A maximum FTL was achieved using the single-point ROI technique, but with a lower inter-operator agreement (ICC = 0.99 vs. 0.83). The ADC and maximum FTL were significantly decreased in patients compared to controls. Conclusion Both ROI localization techniques are feasible to analyze the sciatic nerve in the setting of muscular disease. A maximum FTL is reached using the single-point ROI, however, at the cost of lower inter-operator agreement.

MRI scanner-independent specific absorption rate measurements using diffusion coefficients.

OBJECTIVE: The purpose of this study was to measure specific absorption rate (SAR) during MRI scanning using a human torso phantom through quantification of diffusion coefficients independently of those reported by the scanner software for five 1.5 and 3 T clinical MRI systems from different vendors. METHODS: A quadrature body coil transmitted the RF power and a body array coil received the signals. With diffusion tensor imaging, SAR values for three MRI sequences were measured on the five scanners and compared to the nominal values calculated by the scanners. RESULTS: For the GE 1.5 T MRI system, the MRI scanner-reported SAR value was 1.58 W kg-1 and the measured SAR value was 1.38 W kg-1 . For the Philips 1.5 T MRI scanner, the MRI system-reported SAR value was 1.48 W kg-1 and the measured value was 1.39 W kg-1 . For the Siemens 3 T MRI system, the reported SAR value was 2.5 W kg-1 and the measured SAR value was 1.96 W kg-1 . For two Philips 3 T MRI scanners, the reported SAR values were 1.5 W kg-1 and the measured values were 1.94 and 1.96 W kg-1 . The percentage differences between the measured and reported SAR values on the GE 1.5 T, Philips 1.5 T, Siemens 3 T, and Philips 3 T were 13.5, 6.3, 24.2, 25.6, and 26.6% respectively. CONCLUSION: The scanner-independent SAR measurements using diffusion coefficients described in this study can play a significant role in estimating accurate SAR values as a standardized method.

Assessment of diffusion tensor image quality across sites and vendors using the American College of Radiology head phantom.

The purpose of this study was to explore the feasibility of assessing quality of diffusion tensor imaging (DTI) from multiple sites and vendors using American College of Radiology (ACR) phantom. Participating sites (Siemens (n = 2), GE (n= 2), and Philips (n = 4)) reached consensus on parameters for DTI and used the widely available ACR phantom. Tensor data were processed at one site. B0 and eddy current distortions were assessed using grid line displacement on phantom Slice 5; signal-to-noise ratio (SNR) was measured at the center and periphery of the b = 0 image; fractional anisotropy (FA) and mean diffusivity (MD) were assessed using phantom Slice 7. Variations of acquisition parameters and deviations from specified sequence parameters were recorded. Nonlinear grid line distortion was higher with linear shimming and could be corrected using the 2nd order shimming. Following image registration, eddy current distortion was consistently smaller than acquisi-tion voxel size. SNR was consistently higher in the image periphery than center by a factor of 1.3-2.0. ROI-based FA ranged from 0.007 to 0.024. ROI-based MD ranged from 1.90 × 10-3 to 2.33 × 10-3 mm2/s (median = 2.04 × 10-3 mm2/s). Two sites had image void artifacts. The ACR phantom can be used to compare key qual-ity measures of diffusion images acquired from multiple vendors at multiple sites.

Induced magnetic moment in stainless steel components of orthodontic appliances in 1.5 T MRI scanners.

PURPOSE: Most orthodontic appliances are made of stainless steel materials and induce severe magnetic susceptibility artifacts in brain MRI. In an effort for correcting these artifacts, it is important to know the value of induced magnetic moments in all parts of orthodontic appliances. In this study, the induced magnetic moment of stainless steel orthodontic brackets, molar bands, and arch-wires from several vendors is measured. METHODS: Individual stainless steel brackets, molar bands, and short segments of arch-wire were positioned in the center of spherical flask filled with water through a thin plastic rod. The induced magnetic moment at 1.5 T was determined by fitting the B0 map to the z-component of the magnetic dipole field using a computer routine. RESULTS: The induced magnetic moment at 1.5 T was dominated by the longitudinal component mz, with a small contribution from the transverse components. The mz was insensitive to the orientation of the metal parts. The orthodontic brackets collectively dominated the magnetic dipole moment in orthodontic appliances. In brackets from six vendors, the total induced mz from 20 brackets for nonmolar teeth ranged from 0.108 to 0.158 (median 0.122) A ⋅ m(2). The mz in eight molar bands with bracket attachment from two vendors ranged from 0.0004 to 0.0166 (median 0.0035) A ⋅ m(2). Several full length arch wires had induced magnetic moment in the range of 0.006-0.025 (median 0.015) A ⋅ m(2). CONCLUSIONS: Orthodontic brackets collectively contributed most to the total magnetic moment. Different types of brackets, molar bands, and arch wires all exhibit substantial variability in the induced magnetic moment.

Pancreatic iron and fat assessment by MRI-R2* in patients with iron overload diseases.

BACKGROUND: To determine the pancreatic iron (R2*) and fat content (FC) in comparison to hepatic and cardiac R2* in patients with iron overload disorders like ß-thalassemia major (TM), Diamond-Blackfan anemia (DBA) or hereditary hemochromatosis. METHODS: R2* rates were assessed in the liver, heart and pancreas of 42 patients with TM, 29 subjects with other iron overload diseases, and 10 controls using an ECG-gated breathhold sequence (12 echo time [TE] = 1.3-25.7 ms, readout repetition time [TR] = 244 ms). Pancreatic R2* and FC were assessed from TE dependent region of interest based signal intensities performing water-fat chemical shift relaxometry and were compared with laboratory parameters (glucose, HbA1c, amylase and lipase). RESULTS: A pancreatic iron gradient from tail (R2* = 122 s(-1) ) to head (R2* = 114 s(-1) , P < 10(-4) ) was found. The close association between cardiac and pancreatic R2* was also confirmed in patients with TM and other iron overload diseases (rs = 0.64, P < 10(-4) ). Receiver operator characteristic analysis (area: 0.89, P < 10(-4) ) identified patients with elevated cardiac iron at a pancreatic R2* cut-off level of 131s(-1) (sensitivity = specificity at 81%). Highest pancreatic R2* (211s(-1) ) and FC (36%) were found in the tail region of diabetic patients with TM. CONCLUSION: Pancreatic tail showed highest R2* rates and fat contents, especially in patients with thalassemia. Besides iron accumulation fatty degeneration might be an additional risk factor for the development of diabetes in ß-thalassemia major, but this hypothesis needs further studies in prediabetic patients.

Development of human brain structural networks through infancy and childhood.

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers.

Signal-to-noise assessment for diffusion tensor imaging with single data set and validation using a difference image method with data from a multicenter study.

PURPOSE: To describe a quantitative method for determination of SNR that extracts the local noise level using a single diffusion data set. METHODS: Brain data sets came from a multicenter study (eight sites; three MR vendors). Data acquisition protocol required b=0, 700 s/mm2, fov=256×256 mm2, acquisition matrix size 128×128, reconstruction matrix size 256×256; 30 gradient encoding directions and voxel size 2×2×2 mm3. Regions-of-interest (ROI) were placed manually on the b=0 image volume on transverse slices, and signal was recorded as the mean value of the ROI. The noise level from the ROI was evaluated using Fourier Transform based Butterworth high-pass filtering. Patients were divided into two groups, one for filter parameter optimization (N=17) and one for validation (N=10). Six white matter areas (the genu and splenium of corpus callosum, right and left centrum semiovale, right and left anterior corona radiata) were analyzed. The Bland-Altman method was used to compare the resulting SNR with that from the difference image method. The filter parameters were optimized for each brain area, and a set of "global" parameters was also obtained, which represent an average of all regions. RESULTS: The Bland-Altman analysis on the validation group using "global" filter parameters revealed that the 95% limits of agreement of percent bias between the SNR obtained with the new and the reference methods were -15.5% (median of the lower limit, range [-24.1%, -8.9%]) and 14.5% (median of the higher limits, range [12.7%, 18.0%]) for the 6 brain areas. CONCLUSIONS: An FT-based high-pass filtering method can be used for local area SNR assessment using only one DTI data set. This method could be used to evaluate SNR for patient studies in a multicenter setting.

Postmortem 31P magnetic resonance spectroscopy of the skeletal muscle: α-ATP/Pi ratio as a forensic tool?

PURPOSE: Phosphor magnetic resonance spectroscopy ((31)P MRS) is an established method for metabolic examinations of resting and exercising skeletal muscle. So far, there are few MRS investigations of human corpses. The aim of this study was to investigate the temporal postmortem pattern of phosphor metabolites in the adductor magnus muscle and to check the value of MRS as a forensic tool, especially for the determination of the time of death. MATERIAL AND METHODS: Eight corpses, died of natural cause, were examined (5 males, 3 females; age: 73±7 y, weight 65.8±15.9 kg). A control group of 3 subjects (2 males, 1 female, mean age: 51±24 y, range: 24-69 y, mean body weight: 84.0±16.5 kg) was examined at a single time point as well. (31)P MRS was performed on a 1.5 T MRI (TR 700 ms, TE 0.35 ms, averages 256, flip angle 90°). A standard (31)P/(1)H heart/liver coil was employed (receiver coil diameter 12 cm). The (31)P MRS scans were repeated in intervals of 1 h over a period from 4.5 to 24 h postmortem (p.m.). The core temperature was rectally measured throughout the MRI examination. RESULTS: The mean core temperature decreased from 36.0°C to 25.7°C. In vivo and ex vivo spectra showed characteristic differences, especially the PCr metabolite was no longer detectable after 10 h p.m. The α-ATP/Pi ratio decreased with time from 0.445 to 0.032 over 24 h p.m. CONCLUSION: There is a characteristic postmortem time pattern of the phosphor metabolites. Especially the acquired α-ATP/Pi ratio could be described by a significant exponential time course (r(2)=0.92, p<0.001). (31)P MRS might be added to the postmortem imaging methods.

Diffusion tensor imaging metrics in neonates-a comparison of manual region-of-interest analysis vs. tract-based spatial statistics.

BACKGROUND: Diffusion tensor data can be analyzed using region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). There is essentially no literature validating or comparing these techniques in the neonate. OBJECTIVE: The purpose of this study was to perform a direct comparison of fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) derived using manual ROI analysis and TBSS modified for use in neonates. MATERIALS AND METHODS: This study was IRB-approved. Thirty-nine infants, 32-49 weeks post-conception age, underwent MRI at 3 T. FA, AD and RD of the callosal genu (CG) and splenium (CS) and posterior limbs of both internal capsules (PLIC) were determined using both techniques. Pearson correlation (r) was used to estimate the concordance of tensor metrics derived from these techniques. RESULTS: The r value for FA in the CG, CS and left and right PLIC was 0.88, 0.75, 0.78 and 0.35, respectively. The r value for axial/radial diffusivity in the CG, CS and left and right PLIC was 0.62/0.72, 0.76/0.64, 0.68/0.9 and 0.3/0.72, respectively. The variable concordance results from problems with spatial correspondence of ROI masks between the native space and the FA skeleton. CONCLUSION: Direct comparison between these methodologies shows tensor metrics varied with location and by degree, suggesting the two techniques do not provide consistently comparable results.