Patients with chronic mild or moderate traumatic brain injury have abnormal longitudinal brain volume enlargement more than atrophy

Abstract

Introduction Many studies have found brain atrophy in patients with traumatic brain injury (TBI), but most of those studies examined patients with moderate or severe TBI. A few recent studies in patients with chronic mild or moderate TBI found abnormally large brain volume. Some of these studies used NeuroQuant®, FDA-cleared software for measuring MRI brain volume. It is not known if the abnormal enlargement occurs before or after injury. The purpose of the current study was to test the hypothesis that it occurs after injury. Methods 55 patients with chronic mild or moderate TBI were compared to NeuroQuant® normal controls ( n > 4000) with respect to MRI brain volume change from before injury (time 0 [t0], estimated volume) to after injury (t1, measured volume). A subset of 36 patients were compared to the normal controls with respect to longitudinal change of brain volume after injury from t1 to t2. Results The patients had abnormally fast increase of brain volume for multiple brain regions, including whole brain, cerebral cortical gray matter, and subcortical regions. Discussion This is the first report of extensive abnormal longitudinal brain volume enlargement in patients with TBI. In particular, the findings suggested that the previously reported findings of cross-sectional brain volume abnormal enlargement were due to longitudinal enlargement after, not before, injury. Abnormal longitudinal enlargement of the posterior cingulate cortex correlated with neuropathic headaches, partially replicating a previously reported finding that was associated with neuroinflammation.

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

“…On 02/19/2022, searches were conducted using the term "NeuroQuant" on PubMed (including cross-referenced articles), Google and Google Scholar. 102 published peer-reviewed studies (described below) were identified that supported the reliability and validity of NeuroQuant R for measuring brain volume in neuropsychiatric patients and normal control subjects (see Figure 1) (Brewer, 2009;Brewer et al, 2009;Kovacevic et al, 2009;Brewer, 2010, 2012;Heister et al, 2011;Engedal et al, 2012;Farid et al, 2012;Hampstead et al, 2012Hampstead et al, , 2016Moen et al, 2012;Ross et al, 2012aRoss et al, ,b, 2013aRoss et al, ,b,c, 2014Ross et al, , 2015Ross et al, , 2016Ross et al, , 2018aRoss et al, ,b, 2020Ross et al, , 2021Bahar-Fuchs et al, 2013;Desikan et al, 2013;Hampstead and Brown, 2013;Ong et al, 2013;Rogne et al, 2013Rogne et al, , 2016Brezova et al, 2014;Elvemo et al, 2014Elvemo et al, , 2015England et al, 2014;Evans et al, 2014;Hill et al, 2014;Kjelvik et al, 2014;Okamura et al, 2014;Shoemaker et al, 2014;Ting et al, 2014;Villemagne et al, 2014Villemagne et al, , 2017Yaldizli et al, 2014;Yu et al, 2014;…”

“…NeuroGage R 2.0 was similar to NeuroGage R 1.0 insofar as it continued to provide analyses for asymmetry, longitudinal change and volume estimation (Ross et al, 2018b(Ross et al, , 2021. However, it was improved in several ways: (1) it was based on NeuroQuant R 2.0 analyses instead of 1.0 analyses; (2) it included more brain regions than NeuroGage R 1.0; (3) it included more normal controls (N = 80); and (4) and for determination of the normal relationship between brain volume vs. age across the adult lifespan, it used NeuroQuant R normal control data (N = approximately 4000) instead of data from a previously published meta-analysis of normal control studies that in total had less normal controls (N = 2,211) and that used various volumetric software programs other than NeuroQuant R (Hedman et al, 2012).…”

“…The latest version of NeuroGage R software is 3.0, which is based on NeuroQuant R 3.0 (Ross et al, 2021) (for sample NeuroGage R reports, see online supplementary file: see text footnote 3). Compared to NeuroGage R 2.0, version 3.0 was improved in the following ways:…”

“…The current review will focus on FreeSurfer as a prominent example of these popular research tools, and as the cognate version of NeuroQuant R (see below). We previously compared NeuroQuant R and FreeSurfer (Ross et al, 2018a(Ross et al, , 2021 and will compare them briefly herein (see Table 1). In summary, FreeSurfer is free (as its name implies), flexible and popular in research settings.…”

“…In 2012, NeuroGage R was introduced by the Virginia Institute of Neuropsychiatry. NeuroGage R is a software program that is built on NeuroQuant R and extends its utility in several important ways, including evaluations of the following: (1) asymmetry (Ross et al, 2015(Ross et al, , 2018b; (2) longitudinal change over time (Ross et al, 2012b(Ross et al, , 2013a(Ross et al, , 2015(Ross et al, , 2018b(Ross et al, , 2021; and (3) estimation of brain volume just before injury, based on the patient's age, intracranial volume (measured from a later brain MRI; intracranial volume generally does not change during adulthood), and the known relationship between age, brain volume and intracranial volume during the normal adult lifespan (Ross et al, 2012b(Ross et al, , 2013a(Ross et al, , 2015(Ross et al, , 2016(Ross et al, , 2018b(Ross et al, , 2021.…”