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

Not available.

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.

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.

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.

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 an augmented reality system for tracheal intubation guidance of airway management.

Tracheal intubation is a crucial procedure performed in airway management to sustain life during various procedures. However, difficult airways can make intubation challenging, which is associated with increased mortality and morbidity. This is particularly important for children who undergo intubation where the situation is difficult. Improved airway management will decrease incidences of repeated attempts, decrease hypoxic injuries in patients, and decrease hospital stays, resulting in better clinical outcomes and reduced costs. Currently, 3D printed models based on CT scans and ultrasound-guided intubation are being used or tested for device fitting and procedure guidance to increase the success rate of intubation, but both have limitations. Maintaining a 3D printing facility can be logistically inconvenient, and it can be time consuming and expensive. Ultrasound-guided intubation can be hindered by operator dependence, limited two-dimensional visualization, and potential artifacts. In this study, we developed an augmented reality (AR) system that allows the overlay of intubation tools and internal airways, providing real-time guidance during the procedure. A child manikin was used to develop and test the AR system. Three-dimensional CT images were acquired from the manikin. Different tissues were segmented to generate the 3D models that were imported into Unity to build the holograms. Phantom experiments demonstrated the AR-guided system for potential applications in tracheal intubation guidance.

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.

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.

A quality assurance protocol for diffusion tensor imaging using the head phantom from American College of Radiology.

PURPOSE: To propose a quality assurance procedure for routine clinical diffusion tensor imaging (DTI) using the widely available American College of Radiology (ACR) head phantom. METHODS: Analysis was performed on the data acquired at 1.5 and 3.0 T on whole body clinical MRI scanners using the ACR phantom and included the following: (1) the signal-to-noise ratio (SNR) at the center and periphery of the phantom, (2) image distortion by EPI readout relative to spin echo imaging, (3) distortion of high-b images relative to the b= 0 image caused by diffusion encoding, and (4) determination of fractional anisotropy (FA) and mean diffusivity (MD) measured with region-of-interest (ROI) and pixel-based approaches. Reproducibility of the measurements was assessed by five repetitions of data acquisition on each scanner. RESULTS: The SNR at the phantom center was approximately half of that near the periphery at both 1.5 and 3 T. The image distortion by the EPI readout was up to 7 mm at 1.5 T and 10 mm at 3 T. The typical distortion caused by eddy currents from diffusion encoding was on the order of 0.5 mm. The difference between ROI-based and pixel-based MD quantification was 1.4% at 1.5 T and 0.3% at 3 T. The ROI-based MD values were in close agreement (within 2%) with the reference values. The ROI-based FA values were approximately a factor of 10 smaller than pixel-based values and less than 0.01. The measurement reproducibility was sufficient for quality assurance (QA) purposes. CONCLUSIONS: This QA approach is simple to perform and evaluates key aspects of the scanner performance for DTI data acquisition using a widely available phantom.

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.

Improving SNR of RF coils using composite coil elements.

A composite coil element consists of up to three independent orthogonal loops. It improves the flexibility in shaping the radio frequency (RF) field in its vicinity, compared with a single-loop coil element. Computer simulations were conducted to explore the potential advantages of this type of coil configuration for improving the signal-to- noise ratio (SNR), including the intrinsic SNR (ISNR) and the realistic SNR, when the effects of resistive loss of the coil were included. A 'half-space' model was considered, with a variable B(0) direction relative to the surface of a large conductive medium. The SNR performance of a square single-loop coil parallel to the surface of the medium was compared with that of a composite coil element where up to two additional orthogonal square loops of the same size were added to the single coil loop. The SNR performances of coil arrays consisting of single-loop elements and composite elements were also evaluated. The RF field was calculated using the finite-difference time-domain method. The results show that the composite coil element has a substantially better ISNR at all depths from the surface than that of a single-loop element covering the same surface area. Furthermore, the ISNR of a composite element is not sensitive to the surface orientation relative to the B(0) field. The computer simulation also revealed that at 128 MHz, the resistive loss from the copper coil loops standing upright on the surface at room temperature is substantial compared to the loss in the medium. Consequently, the realistic SNR is significantly lower than ISNR at 128 MHz for a composite coil element. The coil loading by the medium becomes more dominant at 170 and 298 MHz, and the differences between the realistic SNR and ISNR become smaller at these higher frequencies.

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.

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.

Feeling sounds after a thalamic lesion.

OBJECTIVE: The ventrolateral nucleus of the thalamus (VL), based on its connectivity with the cerebellum and motor cortex, has long been considered to be involved with motor functions. We show that the human VL also plays a prominent role in sensory processing. METHODS: Structural magnetic resonance imaging and diffusion tensor imaging were used to localize a small lesion restricted to the right VL in a patient with contralesional sensory processing deficits. Systematic assessments of anatomic brain organization and behavioral measurements of somatosensory and visual processing were conducted at several time points after stroke. RESULTS: Initially, the patient was more likely to detect events on the contralesional side when a simultaneous ipsilesional event was presented within the same, but not different, sensory modality. This perceptual phenomenon, which we refer to as unisensory antiextinction, persisted for several months before transforming into a form of synesthesia in which auditory stimuli produced tactile percepts. Tractography performed on the diffusion tensor imaging data showed altered connections from the lesioned thalamus to the cerebral cortex, suggesting a neural basis for these sensory changes. INTERPRETATION: These results demonstrate a role for the VL in sensory processing and suggest that reorganization of thalamocortical axonal connectivity can lead to major changes in perception.

Towards a complete coil array.

A complete RF coil system, as has been previously defined, is capable of generating any steady-state RF field, at the MR frequency, that is compatible with Maxwell's equations. A coil system is complete if it is capable of generating all basis vector fields in the multipole expansion of the electromagnetic fields. A complete coil system has the potential to reach the ultimate intrinsic signal-to-noise as an MRI receiver coil. It also offers maximum flexibility in tailoring the spatial RF field distribution as an excitation coil. Here, computer simulations have been performed on array coils employing composite coil elements, assuming the current loops are small and can be approximated by magnetic dipoles. We demonstrate that a coil array can be configured to approximate a truncated complete array coil and to generate the basis magnetic vector fields up to certain orders in the multipole expansion of the electromagnetic fields.

Brain proton magnetic resonance spectroscopy and neuromuscular pathology in a patient with GM1 gangliosidosis.

The authors report the clinical, neuroradiologic, and neuromuscular pathological findings in a patient with GM1 gangliosidosis. The proton magnetic resonance spectroscopy, previously reported in a single patient with GM1 gangliosidosis, detected a mild reduction of N-acetylaspartate, consistent with relative paucity of axons and neurons and increased levels of myoinositol suggestive of gliotic white matter changes along with the accumulation of an additional compound that could represent either guanidinoacetate or Gal beta 1-6Gal beta 1-4)GlcNAc, an oligosaccharide previously isolated from the urine of GM1 gangliosidosis patients. Although these findings will have to be further confirmed in more patients with GM1 gangliosidosis, they suggest that proton magnetic resonance spectroscopy may provide useful end points to assess the efficacy of novel treatments that could soon become clinically available. Histologically, no significant alterations were found in axons, but there was evidence of redundant and inappropriately folded myelin, which is a feature attributed to disturbed axon-glial interactions.

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.