Histological Validation of DW-MRI Tractography in Human Postmortem Tissue

Abstract

Despite several previous attempts, histological validation of diffusion-weighted magnetic resonance imaging (DW-MRI)-based tractography as true axonal fiber pathways remains difficult. In the present study, we establish a method to compare histological and tractography data precisely enough for statements on the level of single tractography pathways. To this end, we used carbocyanine dyes to trace connections in human postmortem tissue and aligned them to high-resolution DW-MRI of the same tissue processed within the diffusion tensor imaging (DTI) formalism. We provide robust definitions of sensitivity (true positives) and specificity (true negatives) for DTI tractography and characterize tractography paths in terms of receiver operating characteristics. With sensitivity and specificity rates of approximately 80%, we could show a clear correspondence between histological and inferred tracts. Furthermore, we investigated the effect of fractional anisotropy (FA) thresholds for the tractography and identified FA values between 0.02 and 0.08 as optimal in our study. Last, we validated the course of entire tractography curves to move beyond correctness determination based on pairs of single points on a tract. Thus, histological techniques, in conjunction with alignment and processing tools, may serve as an important validation method of DW-MRI on the level of inferred tractography projections between brain areas.

Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited

“…The tracer-labeled ROIs were transposed to the same space as the DWI data ( Fig. 1), and the agreement between tracer results and tractography results was estimated in terms of sensitivity and specificity (30,31). Additionally, to identify the tractography technique and/or the combination of user-defined tractography parameters that yielded the best overall combination of specificity and sensitivity, we computed the Youden index (J) [(specificity + sensitivity) −1] (32), a widely used measure in the cost-benefit analysis of diagnostic decision-making.…”

Diameter, Length, Speed, and Conduction Delay of Callosal Axons in Macaque Monkeys and Humans: Comparing Data from Histology and Magnetic Resonance Imaging Diffusion Tractography

“…A good correspondence was found between DTT/histology estimates for the following: fibers spread (Kaufman et al, 2005) in the genu of the CC and in the anterior cingulum bundle in prosimians; fiber distribution (Dauguet et al, 2007) in the projection of motor cortex to the internal capsule, in the thalamocortical projection to S1 and in the callosal pathway in macaques; fiber orientation in the genu of the CC and in the gray and white layers of the superior colliculus (Leergaard et al, 2010) of rats; projections from prefrontal, somatosensory, and motor cortex (Dyrby et al, 2007) in minipig; and retino-geniculo-striate and cortico-spinal pathways of gorilla (Kaufman et al, 2010). Histological validation of tractography has also been obtained ex vivo in human by visualization of fiber tracts with injection of carbocyanine and alignment with DTT images (Seehaus et al, 2012). Finally, a recent study comparing DTT and histological data (Jbabdi et al, 2013) has highlighted similarities and differences in the white matter projections of ventral prefrontal cortex in monkeys and humans, providing a validation of tractography results with tracing techniques.…”

Mapping somatosensory connectivity in adult mice using diffusion MRI tractography and super-resolution track density imaging

“…The structural composition and connectivity of the "whisker pathways" has been described using 2D histologic and functional activation methods. Network tracking techniques include lesion studies, (Killackey and Fleming, 1985;Killackey and Leshin, 1975); carbocyanine dyes (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine Perchlorate; DiI, DiA) (Kivrak and Erzurumlu, 2013;Seehaus et al, 2013) and myelin staining (Barrera et al, 2012); these techniques are also complemented by Lenti and Adeno-associated viral vector expression of fluorescent proteins (Aronoff et al, 2010;Dittgen et al, 2004;Wimmer et al, 2010). A range of macroscopic to microscopic functional connectivity mapping techniques include functional MRI (Kim et al, 2012;Yang et al, 1996), 2-photon imaging of electrical activity using voltage-sensitive dyes (Petersen et al, 2003a;Petersen et al, 2003b) and channelrhodopsins to map neuronal connectivity have also been conducted (Paz et al, 2011;Petreanu et al, 2007).…”