Divided and subtracted MRI is a novel imaging processing technique, where the difference of two images is divided by their sum. When the sequence parameters are chosen properly, this results in images with a high T₁ or T₂ weighting over a small range of tissues with specific T₁ and T₂ values. In the T₁ domain, we describe the implementation of the divided Subtracted Inversion Recovery Sequence (dSIR), which is used to image very small changes in T₁ from normal in white matter. dSIR has shown widespread changes in otherwise normal-appearing white matter in patients suffering from mild traumatic brain injury (mTBI), substance abuse, and ischemic leukoencephalopathy. It can also be targeted to measure small changes in T₁ from normal in other tissues. In the T₂ domain, we describe the divided echo subtraction (dES) sequence that is used to image musculoskeletal tissues with a very short T₂*. These tissues include fascia, tendons, and aponeuroses. In this manuscript, we explain how this contrast is generated, review how these techniques are used in our research, and discuss the current challenges and limitations of this technique.

Primary objective: Persistent concussion symptoms (PCS) affect 10–30% of individuals after sports-related concussion. This study evaluated the effect of exercise-based rehabilitation on symptom scores, brain-derived neurotrophic factor (BDNF), cognitive functions and static balance in a sample of participants with PCS. Research design: One group pre-test post-test pilot study. Methods and procedure: Nine participants with PCS received a structured exercise-based rehabilitation program. Changes in symptom scores, BDNF, cognitive functions and measures of static balance were used to evaluate the utility of the exercise program. Main outcome and results: The results of this pilot study indicate a significant improvement in symptom scores following treatment, as well as some associated benefits in regards to cognitive function and static balance. BDNF levels in the participants with PCS within this study are notably lower than in a previous study on healthy controls. Conclusions: The preliminary evidence reported in the current pilot study is clinically relevant as our findings suggest exercise-based treatments may improve PCS outcomes in a more favourable manner than rest-based treatment.

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.

Background: Delayed Post-Hypoxic Leukoencephalopathy (DPHL), or Grinker’s myelinopathy, is a syndrome in which extensive changes are seen in the white matter of the cerebral hemispheres with MRI weeks or months after a hypoxic episode. T₂-weighted spin echo (T₂-wSE) and/or T₂-Fluid Attenuated Inversion Recovery (T₂-FLAIR) images classically show diffuse hyperintensities in white matter which are thought to be near pathognomonic of the condition. The clinical features include Parkinsonism and akinetic mutism. DPHL is generally regarded as a rare condition. Methods and Results: Two cases of DPHL imaged with MRI nine months and two years after probable hypoxic episodes are described. No abnormalities were seen on the T₂-FLAIR images with MRI, but very extensive changes were seen in the white matter of the cerebral and cerebellar hemisphere on divided Subtraction Inversion Recovery (dSIR) images. dSIR sequences may produce ten times the contrast of conventional inversion recovery (IR) sequences from small changes in T₁. The clinical findings in both cases were of cognitive impairment without Parkinsonism or akinetic mutism. Conclusion: The classic features of DPHL may only represent the severe end of a spectrum of diseases in white matter following global hypoxic injury to the brain. The condition may be much more common than is generally thought but may not be recognized using conventional clinical and MRI criteria for diagnosis. Reappraisal of the syndrome of DPHL to include clinically less severe cases and to encompass recent advances in MRI is advocated.