Taylor Emsden

Background Management of patients with persistent or worsening symptoms following traumatic brain injury (TBI) presents difficulties. MRI is usually negative in mild TBI (mTBI) and usually only shows residual quiescent disease in moderate to severe TBI (msTBI). Objective We hypothesize that patients with persistent symptoms from prior TBI will show findings on a divided Subtracted Inversion Recovery (dSIR) sequence that are sensitive to small changes from normal in white matter T₁. Materials and methods Neurologically healthy controls (n = 37) and patients with persistent symptoms following TBI (n = 29) were examined with T₂-FLAIR and dSIR sequences. T₂-FLAIR images were evaluated for minor changes and overt pathology. dSIR images were evaluated for “whiteout signs” defined as widespread, bilateral, and symmetrical high signal in white matter. Odds ratios were calculated for the association between the presence of a whiteout sign and being in the symptomatic group. Results Overt pathology was seen on the T₂-FLAIR images in six msTBI patients and one mTBI patient. No widespread changes were seen on the T₂-FLAIR images in the control or TBI groups. Whiteout signs were seen on the dSIR images in 25 of 29 TBI patients and in three of 37 controls. The whiteout sign was strongly associated with symptomatic TBI status, with odds ratios ≥ 14. The kappa statistic for inter-reader correlation (whiteout sign vs. no whiteout sign) was κ = 0.85. Conclusion The whiteout sign was strongly associated with being in the symptomatic group and is a potential biomarker for recognition of secondary changes to the brain in patients with persistent symptoms following TBI.

In this educational review, the basic physics underlying the use of ultra-high contrast (UHC) bipolar filter (BLAIR) sequences, including divided subtracted inversion recovery (dSIR), is explained. These sequences can increase the contrast produced by small changes in T₁ by a factor of ten or more compared with conventional IR sequences. In illustrative cases, the sequences were used in multiple sclerosis (MS) patients during relapse and remission and were compared with positionally matched conventional (T₂-weighted spin echo, T₂-FLAIR) images. Well-defined focal lesions were seen with dSIR sequences in areas where little or no change was seen with conventional sequences. In addition, widespread abnormalities affecting almost all of the white matter of the brain were seen during relapses when there were no corresponding abnormalities seen on conventional sequences (the whiteout sign). Grayout signs, in which there is a loss of contrast in gray matter or between gray matter and CSF, were also seen, as well as high signal boundaries around lesions. Disruption of the usual high signal boundary between white and gray matter was seen in leucocortical lesions. Lesions in the spinal cord were better seen or only seen with dSIR sequences. Generalized change was observed in the optic nerve with the dSIR sequence in a case of optic neuritis. UHC BLAIR sequences may be of considerable value for recognition of abnormalities in clinical practice and in research studies on MS.

Ultra-high contrast (UHC) MRI describes forms of MRI in which little or no contrast is seen on conventional MRI images but very high contrast is seen with UHC techniques. One of these techniques uses the divided subtracted inversion recovery (dSIR) sequence, which, in modelling studies, can produce ten times the contrast of conventional inversion recovery (IR) sequences. When used in cases of mild traumatic brain injury (mTBI), the dSIR sequence frequently shows extensive abnormalities in white matter that appears normal when imaged with conventional T₂-fluid-attenuated IR (T₂-FLAIR) sequences. The changes are bilateral and symmetrical in white matter of the cerebral and cerebellar hemispheres. They partially spare the anterior and posterior central corpus callosum and peripheral white matter of the cerebral hemispheres and are described as the whiteout sign. In addition to mTBI, the whiteout sign has also been seen in methamphetamine use disorder and Grinker’s myelinopathy (delayed post-hypoxic leukoencephalopathy) in the absence of abnormalities on T₂-FLAIR images, and is a central component of post-insult leukoencephalopathy syndromes. This paper describes the concept of ultra-high contrast MRI, the whiteout sign, the theory underlying the use of dSIR sequences and post-insult leukoencephalopathy syndromes.

In modelling studies targeted MRI (tMRI) of small increases in the T1 of tissues using divided Subtracted Inversion Recovery (dSIR) sequences show ten or more times the contrast seen with conventional IR sequences. This may be particularly useful in imaging normal appearing white matter where there may be small changes in T1 and/or T2 in disease but these changes may be insufficient to produce useful contrast with conventional T2-weighted spin echo (T2-wSE) and T2-FLuid Attenuated Inversion Recovery (T2-FLAIR) sequences. In a case of recurrent mild Traumatic Brain Injury (mTBI), very extensive high contrast abnormalities were seen in white matter using a dSIR sequence that targeted small increases in T1 in areas where no abnormality was apparent with T2-wSE or T2-FLAIR sequences. The increases in T1 may be due to neuroinflammation and/or degeneration which produces the abnormalities seen on the dSIR images. tMRI of normal appearing white matter may have widespread application in clinical MRI of the brain.