Normal pressure hydrocephalus (NPH) is a characteristic condition in which ventriculomegaly occurs in the apparent absence of raised intracranial pressure resulting in a syndrome of gait disturbance, cognitive decline and urinary incontinence that may be remediable with surgical intervention.¹ The complex processes leading to the evolution of the pathology continue to be much debated. There is thought to be an imbalance affecting cerebrospinal fluid dynamics and cerebral blood flow autoregulation, with implications for tissue elasticity and microstructural integrity of the cerebral mantle.² Some, but not all, changes appear to be responsiveness to CSF diversion. The presence of differing patterns of injury, often occurring on a background of concurrent pathologies, provides challenges to imaging-led early diagnosis and prognostication of NPH. We have used diffusion tensor imaging to demonstrate the patterns of white matter injury in NPH pre- and post-shunting and examined trends for good vs. moderate clinical outcome groups.25 participants were recruited (16 normal pressure hydrocephalus patients and 9 age-matched controls). Diffusion tensor imaging was offered pre-operatively and at six months post-intervention in patients. Six key regions-of-interest were chosen to interrogate the relative contributions of axonal disruption, compression and transependymal diffusion to ‘at-risk’ white matter. Differences were examined using comparison of means and the Student’s t-test. We then concurrently examined the full panel of measures (Fractional Anisotropy (FA), Mean Diffusivity (MD), axial diffusivity (L1), radial diffusivity (L2and3)) to generate DTI profiles and further corroborated findings with plots of isotropy (P) vs. anisotropy (Q) as well as tensor stretch curves.^3,4 Unified categorization of outcome was performed using the Black and Cambridge Outcome Scales.40 datasets were available for analysis. The results indicated distinct differences in the responsiveness of white matter injury patterns with shunting. When post-operative scans were compared to pre-operative images, significant reductions in FA were demonstrated in the inferior longitudinal fasciculus (ILF; 0.480 +/- 0.074 vs. 0.545 +/- 0.051 x10^-4mm²/s) and the posterior limb of the internal capsule (PLIC; 0.665 +/- 0.079 vs. 0.751 +/- 0.034 x10^-4mm²/s); percentage differences of -11.9% and -11.5%; p < 0.05 respectively). DTI profiles for both tracts confirmed changes in DTI measures consistent with improvement in stretch/compression (reductions of axial diffusivity for ILF (12.184 +/- 1.199 vs. 13.040 +/- 1.377 x10^-4mm²/s) and PLIC (11.350 +/- 0.986 vs. 12.377 +/- 1.011 x10^-4mm²/s); percentage differences of -6.6% and -8.3% respectively, along with increases in radial diffusivity for ILF (5.919 +/- 1.242 vs. 5.191 +/- 0.547 x10^-4mm²/s) and PLIC (3.964 +/- 2.131 vs. 3.255 +/- 2.013 x10^-4mm²/s); percentage differences of +14.0% and +21.7% respectively). Significant changes were demonstrated in the ILF and PLIC for the patients with good outcome after shunting. In PLIC, significant changes for the good outcome group were found in both axial (11.225 +/-1.031 vs. 12.292 +/- 1.095 x10^-4mm²/s) and radial (3.544 +/- 0.925 vs. 2.715 +/- 0.289 x10^-4mm²/s) diffusivities; percentage differences of -8.7% and +30.5%, p < 0.05 respectively vs. axial (11.891 +/- 0.603 vs. 12.747 +/- 0.477 x10^-4mm²/s) and radial (5.788 +/-4 .772 vs. 5.594 +/- 4.448 x10^-4mm²/s) diffusivities for the moderate outcome group; percentage differences of -6.7% and +3.5% respectively, non-significant. By contrast, changes in the anterior thalamic radiation demonstrated that the DTI profiles worsened despite surgical intervention. There was a striking increase in post-operative vs. pre-operative axial diffusivity seen in the moderate outcome group of (11.590 +/- 2.734 vs. 9.997 +/- 0.663 x10^-4mm²/s; percentage difference of +15.9% vs. 10.137 +/- 0.626 vs. 10.052 +/- 0.571 x10^-4mm²/s; percentage difference of +0.8% for the good outcome group. This was accompanied by an increase in radial diffusivity (7.331 +/- 2.835 vs. 6.077 +/- 0.658 x10^-4mm²/s; percentage difference of +20.6%) in the moderate outcome group vs. the good outcome group (5.921 +/- 1.705 vs. 5.425 +/- 0.392 x10^-4mm²/s; percentage difference of +9.1%). Changes graphed in the P,Q plane confirmed continuing evidence of axonal disruption despite intervention, with only changes in PLIC sufficiently significant to change the post-operative route of the ROI within the plane towards normalization.DTI profiles and P,Q plots confirmed that NPH patients did not return to normal despite good outcome post-intervention. There was evidence of continuing axonal disruption with mean diffusivities remaining unchanged for all tracts in both clinical outcome groups despite shunting. Tracts relatively remote to the ventricles, such as PLIC, were more amenable to changes in DTI profiles consistent with significant improvement in stretch/compression. Moderate outcome appeared to be characterized by worsening of injury patterns post-intervention. Further work is required to understand if such trends relate to responsiveness of different white matter injury patterns to shunting.