Comparison of Inter-Method Agreement and Reliability for Automatic Brain Volumetry Using Three Different Clinically Available Software Packages.

Background and Objectives: No comparative study has evaluated the inter-method agreement and reliability between Heuron AD and other clinically available brain volumetric software packages. Hence, we aimed to investigate the inter-method agreement and reliability of three clinically available brain volumetric software packages: FreeSurfer (FS), NeuroQuant® (NQ), and Heuron AD (HAD). Materials and Methods: In this study, we retrospectively included 78 patients who underwent conventional three-dimensional (3D) T1-weighed imaging (T1WI) to evaluate their memory impairment, including 21 with normal objective cognitive function, 24 with mild cognitive impairment, and 33 with Alzheimer's disease (AD). All 3D T1WI scans were analyzed using three different volumetric software packages. Repeated-measures analysis of variance, intraclass correlation coefficient, effect size measurements, and Bland-Altman analysis were used to evaluate the inter-method agreement and reliability. Results: The measured volumes demonstrated substantial to almost perfect agreement for most brain regions bilaterally, except for the bilateral globi pallidi. However, the volumes measured using the three software packages showed significant mean differences for most brain regions, with consistent systematic biases and wide limits of agreement in the Bland-Altman analyses. The pallidum showed the largest effect size in the comparisons between NQ and FS (5.20-6.93) and between NQ and HAD (2.01-6.17), while the cortical gray matter showed the largest effect size in the comparisons between FS and HAD (0.79-1.91). These differences and variations between the software packages were also observed in the subset analyses of 45 patients without AD and 33 patients with AD. Conclusions: Despite their favorable reliability, the software-based brain volume measurements showed significant differences and systematic biases in most regions. Thus, these volumetric measurements should be interpreted based on the type of volumetric software used, particularly for smaller structures. Moreover, users should consider the replaceability-related limitations when using these packages in real-world practice.

Hippocampal Atrophy Subtypes of Alzheimer's Disease Using Automatic MRI in a Memory Clinic Cohort: Clinical Implications.

INTRODUCTION: One pathological hallmark of Alzheimer's disease (AD) is atrophy of medial temporal brain regions that can be visualized on magnetic resonance imaging (MRI), but not all patients will have atrophy. The aim was to use MRI to categorize patients according to their hippocampal atrophy status and to present prevalence of the subtypes, difference in clinical symptomatology and progression, and factors associated with hippocampal subtypes. METHODS: We included 215 patients with AD who had been assessed with the clinically available MRI software NeuroQuant (NQ; CorTechs labs/University of California, San Diego, CA, USA). NQ measures the hippocampus volume and calculates a normative percentile. Atrophy was regarded to be present if the percentile was ≤5. Demographics, cognitive measurements, AD phenotypes, apolipoprotein E status, and results from cerebrospinal fluid and amyloid positron emission tomography analyses were included as explanatory variables of the hippocampal subtypes. RESULTS: Of all, 60% had no hippocampal atrophy. These patients were younger and less cognitively impaired concerning global measures, memory function, and abstraction but impaired concerning executive, visuospatial, and semantic fluency, and more of them had nonamnestic AD, compared to those with hippocampal atrophy. No difference in progression rate was observed between the two groups. In mild cognitive impairment patients, amyloid pathology was associated with the no hippocampal atrophy group. CONCLUSION: The results have clinical implications. Clinicians should be aware of the large proportion of AD patients presenting without atrophy of the hippocampus as measured with this clinical MRI method in the diagnostic set up and that nonamnestic phenotypes are more common in this group as compared to those with atrophy. Furthermore, the findings are relevant in clinical trials.

Diagnosis of Hippocampal Sclerosis in Children: Comparison of Automated Brain MRI Volumetry and Readers of Varying Experience.

BACKGROUND. Hippocampal sclerosis (HS) is a leading cause of medically refractory temporal lobe epilepsy in children. The diagnosis is clinically important because most patients with HS have good postsurgical outcomes. OBJECTIVE. This study aimed to compare the performance of a fully automated brain MRI volumetric tool and readers of varying experience in the diagnosis of pediatric HS. METHODS. This retrospective study included 22 children with HS diagnosed between January 2009 and January 2020 who underwent surgery and an age- and sex-matched control group of 44 patients with normal MRI findings and extratemporal epilepsy diagnosed between January 2009 and January 2020. Regional brain MRI volumes were calculated from a high-resolution 3D T1-weighted sequence using an automated volumetric tool. Four readers (two pediatric radiologists [experienced] and two radiology residents [inexperienced]) visually assessed each MRI examination to score the likelihood of HS. One inexperienced reader repeated the evaluations using the volumetric tool. The area under the ROC curve (AUROC), sensitivity, and specificity for HS were computed for the volumetric tool and the readers. Diagnostic performances were compared using McNemar tests. RESULTS. In the HS group, the hippocampal volume (affected vs unaffected, 3.54 vs 4.59 cm3) and temporal lobe volume (affected vs unaffected, 5.66 vs 6.89 cm3) on the affected side were significantly lower than on the unaffected side (p < .001) using the volu-metric tool. AUROCs of the volumetric tool were 0.813-0.842 in patients with left HS and 0.857-0.980 in patients with right HS (sensitivity, 81.8-90.9%; specificity, 70.5-95.5%). No significant difference (p = .63 to > .99) was observed between the performance of the volumetric tool and the performance of the two experienced readers as well as one inexperienced reader (AUROCs for these three readers, 0.968-0.999; sensitivity, 86.4-90.9%; specificity, 100.0%). The volumetric tool had better performance (p < .001) than the other inexperienced reader (AUROC, 0.806; sensitivity, 81.8%; specificity, 47.7%). With subsequent use of the tool, this inexperienced reader showed a nonsignificant increase (p = .10) in AUROC (0.912) as well as in sensitivity (86.4%) and specificity (84.1%). CONCLUSION. A fully automated volumetric brain MRI tool outperformed one of two inexperienced readers and performed as well as two experienced readers in identifying and lateralizing HS in pediatric patients. The tool improved the performance of an inexperienced reader. CLINICAL IMPACT. A fully automated volumetric tool facilitates diagnosis of HS in pediatric patients, especially for an inexperienced reader.

Visual versus Verbal Working Memory in Statistically Determined Patients with Mild Cognitive Impairment: On behalf of the Consortium for Clinical and Epidemiological Neuropsychological Data Analysis (CENDA).

OBJECTIVE: Previous research in mild cognitive impairment (MCI) suggests that visual episodic memory impairment may emerge before analogous verbal episodic memory impairment. The current study examined working memory (WM) test performance in MCI to assess whether patients present with greater visual versus verbal WM impairment. WM performance was also assessed in relation to hippocampal occupancy (HO), a ratio of hippocampal volume to ventricular dilation adjusted for demographic variables and intracranial volume. METHODS: Jak et al. (2009) (The American Journal of Geriatric Psychiatry, 17, 368-375) and Edmonds, Delano-Wood, Galasko, Salmon, & Bondi (2015) (Journal of Alzheimer's Disease, 47(1), 231-242) criteria classify patients into four groups: little to no cognitive impairment (non-MCI); subtle cognitive impairment (SCI); amnestic MCI (aMCI); and a combined mixed/dysexecutive MCI (mixed/dys MCI). WM was assessed using co-normed Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backwards and Wechsler Memory Scale-IV (WMS-IV) Symbol Span Z-scores. RESULTS: Between-group analyses found worse WMS-IV Symbol Span and WAIS-IV Digit Span Backwards performance for mixed/dys MCI compared to non-MCI patients. Within-group analyses found no differences for non-MCI patients; however, all other groups scored lower on WMS-IV Symbol Span than WAIS-IV Digit Span Backwards. Regression analysis with HO as the dependent variable was statistically significant for WMS-IV Symbol Span performance. WAIS-IV Digit Span Backwards performance failed to reach statistical significance. CONCLUSIONS: Worse WMS-IV Symbol Span performance was observed in patient groups with measurable neuropsychological impairment and better WMS-IV Symbol Span performance was associated with higher HO ratios. These results suggest that visual WM may be particularly sensitive to emergent illness compared to analogous verbal WM tests.

Comparison of automated volumetry of the hippocampus using NeuroQuant® and visual assessment of the medial temporal lobe in Alzheimer's disease.

Background Different clinically feasible methods for evaluation of medial temporal lobe atrophy exists and are useful in diagnostic work-up of Alzheimer's disease (AD). Purpose To compare the diagnostic properties of two clinically available magnetic resonance imaging (MRI)-based methods-an automated volumetric software, NeuroQuant® (NQ) (evaluation of hippocampus volume) and the Scheltens scale (visual evaluation of medial temporal lobe atrophy [MTA])-in patients with AD dementia, and subjective and mild cognitive impairment (non-dementia). Material and Methods MRIs from 56 patients (31 AD, 25 non-dementia) were assessed with both methods. Correlations between the methods were calculated and receiver operating curve (ROC) analyses that yield area under the curve (AUC) statistics were conducted. Results High correlations were found between the two MRI assessments for the total hippocampal volume measured with NQ and mean MTA score (-0.753, P < 0.001), for the right (-0.767, P < 0.001), and for the left (-0.675, P < 0.001) sides. The NQ total measure yielded somewhat higher AUC (0.88, "good") compared to the MTA mean measure (0.80, "good") in the comparison of patients with AD and non-dementia, but the accuracy was in favor of the MTA scale. Conclusion The two methods correlated highly and both methods reached equally "good" power.

NeuroQuant® and NeuroGage® reveal effects of traumatic brain injury on brain volume.

This report describes the case of a 58-year-old man with moderate traumatic brain injury (TBI) and pre-accident brain disorders who had multiple persistent neuropsychiatric symptoms. NeuroQuant® 2.0 and NeuroGage® 2.0 MRI brain volume analyses were used during the chronic stage of injury (> 1 year after injury) to help understand the effects of the TBI on his brain volume. NeuroQuant® showed widespread cross-sectional atrophy, especially in the frontal and temporal lobes, consistent with encephalomalacia seen on the MRIs. Several of his clinical symptoms were consistent with the volume abnormalities. NeuroGage® longitudinal analyses of volume change from the time 1 to time 2 magnetic resonance imaging showed abnormally rapid atrophy and ventricular enlargement. The high rates of volume change were much more consistent with the relatively recent effects of TBI than with effects of the much more chronic pre-accident brain disorders.

Back to the future: estimating pre-injury brain volume in patients with traumatic brain injury.

INTRODUCTION: A recent meta-analysis by Hedman et al. allows for accurate estimation of brain volume changes throughout the life span. Additionally, Tate et al. showed that intracranial volume at a later point in life can be used to estimate reliably brain volume at an earlier point in life. These advancements were combined to create a model which allowed the estimation of brain volume just prior to injury in a group of patients with mild or moderate traumatic brain injury (TBI). This volume estimation model was used in combination with actual measurements of brain volume to test hypotheses about progressive brain volume changes in the patients. METHODS: Twenty six patients with mild or moderate TBI were compared to 20 normal control subjects. NeuroQuant® was used to measure brain MRI volume. Brain volume after the injury (from MRI scans performed at t1 and t2) was compared to brain volume just before the injury (volume estimation at t0) using longitudinal designs. Groups were compared with respect to volume changes in whole brain parenchyma (WBP) and its 3 major subdivisions: cortical gray matter (GM), cerebral white matter (CWM) and subcortical nuclei+infratentorial regions (SCN+IFT). RESULTS: Using the normal control data, the volume estimation model was tested by comparing measured brain volume to estimated brain volume; reliability ranged from good to excellent. During the initial phase after injury (t0-t1), the TBI patients had abnormally rapid atrophy of WBP and CWM, and abnormally rapid enlargement of SCN+IFT. Rates of volume change during t0-t1 correlated with cross-sectional measures of volume change at t1, supporting the internal reliability of the volume estimation model. A logistic regression analysis using the volume change data produced a function which perfectly predicted group membership (TBI patients vs. normal control subjects). CONCLUSIONS: During the first few months after injury, patients with mild or moderate TBI have rapid atrophy of WBP and CWM, and rapid enlargement of SCN+IFT. The magnitude and pattern of the changes in volume may allow for the eventual development of diagnostic tools based on the volume estimation approach.

Regional MRI volumetry using NeuroQuant versus visual rating scales in patients with cognitive impairment and dementia.

BACKGROUND AND PURPOSE: The aims were to compare the novel regional brain volumetric measures derived by the automatic software NeuroQuant (NQ) with clinically used visual rating scales of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal (GCA-f), and posterior atrophy (PA) brain regions, assessing their diagnostic validity, and to explore if combining automatic and visual methods would increase diagnostic prediction accuracy. METHODS: Brain magnetic resonance imaging (MRI) examinations from 86 patients with subjective and mild cognitive impairment (i.e., non-dementia, n = 41) and dementia (n = 45) from the Memory Clinic at Oslo University Hospital were assessed using NQ volumetry and with visual rating scales. Correlations, receiver operating characteristic analyses calculating area under the curves (AUCs) for diagnostic accuracy, and logistic regression analyses were performed. RESULTS: The correlations between NQ volumetrics and visual ratings of corresponding regions were generally high between NQ hippocampi/temporal volumes and MTA (r = -0.72/-0.65) and between NQ frontal volume and GCA-f (r = -0.62) but lower between NQ parietal/occipital volumes and PA (r = -0.49/-0.37). AUCs of each region, separating non-dementia from dementia, were generally comparable between the two methods, except that NQ hippocampi volume did substantially better than visual MTA (AUC = 0.80 vs. 0.69). Combining both MRI methods increased only the explained variance of the diagnostic prediction substantially regarding the posterior brain region. CONCLUSIONS: The findings of this study encourage the use of regional automatic volumetry in locations lacking neuroradiologists with experience in the rating of atrophy typical of neurodegenerative diseases, and in primary care settings.

Clinically feasible automated MRI volumetry of the brain as a prognostic marker in subjective and mild cognitive impairment.

Background/aims: The number of patients suffering from cognitive decline and dementia increases, and new possible treatments are being developed. Thus, the need for time efficient and cost-effective methods to facilitate an early diagnosis and prediction of future cognitive decline in patients with early cognitive symptoms is becoming increasingly important. The aim of this study was to evaluate whether an MRI based software, NeuroQuant® (NQ), producing volumetry of the hippocampus and whole brain volume (WBV) could predict: (1) conversion from subjective cognitive decline (SCD) at baseline to mild cognitive impairment (MCI) or dementia at follow-up, and from MCI at baseline to dementia at follow-up and (2) progression of cognitive and functional decline defined as an annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. Methods: MRI was performed in 156 patients with SCD or MCI from the memory clinic at Oslo University Hospital (OUH) that had been assessed with NQ and had a clinical follow-up examination. Logistic and linear regression analyses were performed with hippocampus volume and WBV as independent variables, and conversion or progression as dependent variables, adjusting for demographic and other relevant covariates including Mini-Mental State Examination-Norwegian Revised Version score (MMSE-NR) and Apolipoprotein E ɛ4 (APOE ɛ4) carrier status. Results: Hippocampus volume, but not WBV, was associated with conversion to MCI or dementia, but neither were associated with conversion when adjusting for MMSE-NR. Both hippocampus volume and WBV were associated with progression as measured by the annual change in CDR-SB score in both unadjusted and adjusted analyses. Conclusion: The results indicate that automated regional MRI volumetry of the hippocampus and WBV can be useful in predicting further cognitive decline in patients with early cognitive symptoms.

Reliability of automated brain volumetric analysis: A test by comparing NeuroQuant and volBrain software.

BACKGROUND AND PURPOSE: Brain volume analysis from magnetic resonance imaging (MRI) is gaining an important role in neurological diagnosis. This study compares the volumes of brain segments measured by two automated brain analysis software, NeuroQuant (NQ), and volBrain (VB) in order to test their reliability in brain volumetry. METHODS: Using NQ and VB software, the same brain segment volumes were calculated and compared, taken from 56 patients scanned under the same MRI sequence. These segments were intracranial cavity, putamen, thalamus, amygdala, whole brain, cerebellum, white matter, and hippocampus. The paired t-test method has been used to determine if there was a significant difference in these measurements. The interclass correlation (ICC) is used to test inter-method reliability between the two software. Finally, regression analysis was used to examine the possibility of linear correlation. RESULTS: In all brain segments tested but hippocampus, significant differences were found. ICC presents satisfactory to excellent reliability in all brain segments except thalamus and amygdala for which reliability has been proven to be poor. In most cases, linear correlation was found. CONCLUSIONS: The significant differences found in the majority of the tested brain segments are raising questions about the reliability of automated brain analysis as a quantitative tool. Strong linear correlation of the volumetric measurements and good reliability indicates that, each software provides good qualitative information of brain structures size.

Journey to the other side of the brain: asymmetry in patients with chronic mild or moderate traumatic brain injury.

Aim: Patients with chronic mild or moderate traumatic brain injury have some regions of brain atrophy (including cerebral white matter) but even more regions of abnormal brain enlargement (including other cerebral regions). Hypothesis: Ipsilateral injury and atrophy cause the eventual development of contralateral compensatory hypertrophy. Materials & methods: 50 patients with mild or moderate traumatic brain injury were compared to 80 normal controls (n = 80) with respect to MRI brain volume asymmetry. Asymmetry-based correlations were used to test the primary hypothesis. Results: The group of patients had multiple regions of abnormal asymmetry. Conclusion: The correlational analyses supported the conclusion that acute injury to ipsilateral cerebral white matter regions caused atrophy, leading eventually to abnormal enlargement of contralateral regions due to compensatory hypertrophy.

Agreement and Reliability between Clinically Available Software Programs in Measuring Volumes and Normative Percentiles of Segmented Brain Regions.

OBJECTIVE: To investigate the agreement and reliability of estimating the volumes and normative percentiles (N%) of segmented brain regions among NeuroQuant (NQ), DeepBrain (DB), and FreeSurfer (FS) software programs, focusing on the comparison between NQ and DB. MATERIALS AND METHODS: Three-dimensional T1-weighted images of 145 participants (48 healthy participants, 50 patients with mild cognitive impairment, and 47 patients with Alzheimer's disease) from a single medical center (SMC) dataset and 130 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset were included in this retrospective study. All images were analyzed with DB, NQ, and FS software to obtain volume estimates and N% of various segmented brain regions. We used Bland-Altman analysis, repeated measures ANOVA, reproducibility coefficient, effect size, and intraclass correlation coefficient (ICC) to evaluate inter-method agreement and reliability. RESULTS: Among the three software programs, the Bland-Altman plot showed a substantial bias, the ICC showed a broad range of reliability (0.004-0.97), and repeated-measures ANOVA revealed significant mean volume differences in all brain regions. Similarly, the volume differences of the three software programs had large effect sizes in most regions (0.73-5.51). The effect size was largest in the pallidum in both datasets and smallest in the thalamus and cerebral white matter in the SMC and ADNI datasets, respectively. N% of NQ and DB showed an unacceptably broad Bland-Altman limit of agreement in all brain regions and a very wide range of ICC values (-0.142-0.844) in most brain regions. CONCLUSION: NQ and DB showed significant differences in the measured volume and N%, with limited agreement and reliability for most brain regions. Therefore, users should be aware of the lack of interchangeability between these software programs when they are applied in clinical practice.

Updated Review of the Evidence Supporting the Medical and Legal Use of NeuroQuant® and NeuroGage® in Patients With Traumatic Brain Injury.

Over 40 years of research have shown that traumatic brain injury affects brain volume. However, technical and practical limitations made it difficult to detect brain volume abnormalities in patients suffering from chronic effects of mild or moderate traumatic brain injury. This situation improved in 2006 with the FDA clearance of NeuroQuant®, a commercially available, computer-automated software program for measuring MRI brain volume in human subjects. More recent strides were made with the introduction of NeuroGage®, commercially available software that is based on NeuroQuant® and extends its utility in several ways. Studies using these and similar methods have found that most patients with chronic mild or moderate traumatic brain injury have brain volume abnormalities, and several of these studies found-surprisingly-more abnormal enlargement than atrophy. More generally, 102 peer-reviewed studies have supported the reliability and validity of NeuroQuant® and NeuroGage®. Furthermore, this updated version of a previous review addresses whether NeuroQuant® and NeuroGage® meet the Daubert standard for admissibility in court. It concludes that NeuroQuant® and NeuroGage® meet the Daubert standard based on their reliability, validity, and objectivity. Due to the improvements in technology over the years, these brain volumetric techniques are practical and readily available for clinical or forensic use, and thus they are important tools for detecting signs of brain injury.

Comparison of Automated Brain Volume Measures by NeuroQuant vs. Freesurfer in Patients with Mild Cognitive Impairment: Effect of Slice Thickness.

PURPOSE: This study aimed to examine the inter-method reliability and volumetric differences between NeuroQuant (NQ) and Freesurfer (FS) using T1 volume imaging sequence with different slice thicknesses in patients with mild cognitive impairment (MCI). MATERIALS AND METHODS: This retrospective study enrolled 80 patients diagnosed with MCI at our memory clinic. NQ and FS were used for volumetric analysis of three-dimensional T1-weighted images with slice thickness of 1 and 1.2 mm. Inter-method reliability was measured with Pearson correlation coefficient (r), intraclass correlation coefficient (ICC), and effect size (ES). RESULTS: Overall, NQ volumes were larger than FS volumes in several locations: whole brain (0.78%), cortical gray matter (5.34%), and white matter (2.68%). Volume measures by NQ and FS showed good-to-excellent ICCs with both 1 and 1.2 mm slice thickness (ICC=0.75-0.97, ES=-1.0-0.73 vs. ICC=0.78-0.96, ES=-0.9-0.77, respectively), except for putamen, pallidum, thalamus, and total intracranial volumes. The ICCs in all locations, except the putamen and cerebellum, were slightly higher with a slice thickness of 1 mm compared to those of 1.2 mm. CONCLUSION: Inter-method reliability between NQ and FS was good-to-excellent in most regions with improvement with a 1-mm slice thickness. This finding indicates that the potential effects of slice thickness should be considered when performing volumetric measurements for cognitive impairment.

Clinically Available Software for Automatic Brain Volumetry: Comparisons of Volume Measurements and Validation of Intermethod Reliability.

OBJECTIVE: To compare two clinically available MR volumetry software, NeuroQuant® (NQ) and Inbrain® (IB), and examine the inter-method reliabilities and differences between them. MATERIALS AND METHODS: This study included 172 subjects (age range, 55-88 years; mean age, 71.2 years), comprising 45 normal healthy subjects, 85 patients with mild cognitive impairment, and 42 patients with Alzheimer's disease. Magnetic resonance imaging scans were analyzed with IB and NQ. Mean differences were compared with the paired t test. Inter-method reliability was evaluated with Pearson's correlation coefficients and intraclass correlation coefficients (ICCs). Effect sizes were also obtained to document the standardized mean differences. RESULTS: The paired t test showed significant volume differences in most regions except for the amygdala between the two methods. Nevertheless, inter-method measurements between IB and NQ showed good to excellent reliability (0.72 < r < 0.96, 0.83 < ICC < 0.98) except for the pallidum, which showed poor reliability (left: r = 0.03, ICC = 0.06; right: r = -0.05, ICC = -0.09). For the measurements of effect size, volume differences were large in most regions (0.05 < r < 6.15). The effect size was the largest in the pallidum and smallest in the cerebellum. CONCLUSION: Comparisons between IB and NQ showed significantly different volume measurements with large effect sizes. However, they showed good to excellent inter-method reliability in volumetric measurements for all brain regions, with the exception of the pallidum. Clinicians using these commercial software should take into consideration that different volume measurements could be obtained depending on the software used.

Assessment of White Matter Integrity after Pediatric Traumatic Brain Injury.

White matter (WM) abnormalities, such as atrophy and hyperintensities (WMH), can be accessed via magnetic resonance imaging (MRI) after pediatric traumatic brain injury (TBI). Several methods are available to classify WM abnormalities (i.e., total WM volumes and WMHs), but automated and manual volumes and clinical ratings have yet to be compared in pediatric TBI. In addition, WM integrity has been associated reliably with processing speed. Consequently, methods of assessing WM integrity should relate to processing speed to have clinical application. This study had two goals: (1) to compare Scheltens rating scale, manual tracing, FreeSurfer, and NeuroQuant® methods of assessing WM abnormalities, and (2) to relate WM methods to processing speed scores. We report findings from the Social Outcomes of Brain Injury in Kids (SOBIK) study, a multi-center study of 60 children with chronic TBI (65% male) from ages 8-13. Scheltens WMH ratings had good to excellent agreement with WMH volumes for both NeuroQuant (ICC = 0.62; r = 0.29, p = 0.005) and manual tracing (ICC = 0.82; r = 0.50, p = 0.000). NeuroQuant WMH volumes did not correlate with manually traced WMH volumes (r = 0.12, p = 0.21) and had poor agreement (ICC = 0.24). NeuroQuant and FreeSurfer total WM volumes correlated (r = 0.38, p = 0.004) and had fair agreement (ICC = 0.52). The WMH assessment methods, both ratings and volumes, were associated with processing speed scores. In contrast, total WM volume was not related to processing speed. Measures of WMH may hold clinical utility for predicting cognitive functioning after pediatric TBI.

Subcortical volumetric differences between clinical stages of young people with affective and psychotic disorders.

The aim of this study was to investigate differences in subcortical and hippocampal volumes between healthy controls, young people at an early stage of affective and psychotic disorders and those in more advanced stages, to identify markers associated with functional outcomes and illness severity. Young people presenting to youth mental health services with admixtures of depressive, manic and psychotic symptoms (n = 141), and healthy counterparts (n = 49), aged 18-25 were recruited. Participants underwent magnetic resonance imaging, clinical assessments and were rated as to their current clinical stage. Eighty-four patients were classified at the attenuated syndrome stage (Stage 1b) and 57 were classified as having discrete and persistent disorders (Stage 2+). Automated segmentation was performed using NeuroQuant® to determine volumes of subcortical and hippocampus structures which were compared between groups and correlated with clinical and functional outcomes. Compared to healthy controls, Stage 2+ patients showed significantly reduced right amygdala volumes. Whereas Stage 1b patients showed significantly reduced left caudate volumes compared to healthy controls. Smaller left caudate volume correlated with greater psychological distress and impaired functioning. This study shows a clinical application for an automated program to identify and track subcortical changes evident in young people with emerging psychopathology.

Comparing Two Processing Pipelines to Measure Subcortical and Cortical Volumes in Patients with and without Mild Traumatic Brain Injury.

PURPOSE: To compare volumetric results from NeuroQuant® and FreeSurfer in a service member setting. Since the advent of medical imaging, quantification of brain anatomy has been a major research and clinical effort. Rapid advancement of methods to automate quantification and to deploy this information into clinical practice has surfaced in recent years. NeuroQuant® is one such tool that has recently been used in clinical settings. Accurate volumetric data are useful in many clinical indications; therefore, it is important to assess the intermethod reliability and concurrent validity of similar volume quantifying tools. METHODS: Volumetric data from 148 U.S. service members across three different experimental groups participating in a study of mild traumatic brain injury (mTBI) were examined. Groups included mTBI (n = 71), posttraumatic stress disorder (n = 22), or a noncranial orthopedic injury (n = 55). Correlation coefficients and nonparametric group mean comparisons were used to assess reliability and concurrent validity, respectively. RESULTS: Comparison of these methods across our entire sample demonstrates generally fair to excellent reliability as evidenced by large intraclass correlation coefficients (ICC = .4 to .99), but little concurrent validity as evidenced by significantly different Mann-Whitney U comparisons for 26 of 30 brain structures measured. CONCLUSION: While reliability between the two segmenting tools is fair to excellent, volumetric outcomes are statistically different between the two methods. As suggested by both developers, structure segmentation should be visually verified prior to clinical use and rigor should be used when interpreting results generated by either method.

Comparison of Automated Brain Volume Measures obtained with NeuroQuant and FreeSurfer.

PURPOSE: To examine intermethod reliabilities and differences between FreeSurfer and the FDA-cleared congener, NeuroQuant, both fully automated methods for structural brain MRI measurements. MATERIALS AND METHODS: MRI scans from 20 normal control subjects, 20 Alzheimer's disease patients, and 20 mild traumatically brain-injured patients were analyzed with NeuroQuant and with FreeSurfer. Intermethod reliability was evaluated. RESULTS: Pairwise correlation coefficients, intraclass correlation coefficients, and effect size differences were computed. NeuroQuant versus FreeSurfer measures showed excellent to good intermethod reliability for the 21 regions evaluated (r: .63 to .99/ICC: .62 to .99/ES: -.33 to 2.08) except for the pallidum (r/ICC/ES = .31/.29/-2.2) and cerebellar white matter (r/ICC/ES = .31/.31/.08). Volumes reported by NeuroQuant were generally larger than those reported by FreeSurfer with the whole brain parenchyma volume reported by NeuroQuant 6.50% larger than the volume reported by FreeSurfer. There was no systematic difference in results between the 3 subgroups. CONCLUSION: NeuroQuant and FreeSurfer showed good to excellent intermethod reliability in volumetric measurements for all brain regions examined with the only exceptions being the pallidum and cerebellar white matter. This finding was robust for normal individuals, patients with Alzheimer's disease, and patients with mild traumatic brain injury.

Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation.