Chiari type 1 malformation is a neurological disorder characterized by an obstruction of the cerebrospinal fluid (CSF) circulation between the brain (intracranial) and spinal cord (spinal) ...compartments. Actions such as coughing might evoke spinal cord complications in patients with Chiari type 1 malformation, but the underlying mechanisms are not well understood. More insight into the impact of the obstruction on local and overall CSF dynamics can help reveal these mechanisms. Therefore, our previously developed computational fluid dynamics framework was used to establish a subject-specific model of the intracranial and upper spinal CSF space of a healthy control. In this model, we emulated a single cough and introduced porous zones to model a posterior (OBS-1), mild (OBS-2), and severe posterior-anterior (OBS-3) obstruction. OBS-1 and OBS-2 induced minor changes to the overall CSF pressures, while OBS-3 caused significantly larger changes with a decoupling between the intracranial and spinal compartment. Coughing led to a peak in overall CSF pressure. During this peak, pressure differences between the lateral ventricles and the spinal compartment were locally amplified for all degrees of obstruction. These results emphasize the effects of coughing and indicate that severe levels of obstruction lead to distinct changes in intracranial pressure.
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 T
or T
weighting over a small range of tissues with specific T
and T
values. In the T
domain, we describe the implementation of the divided Subtracted Inversion Recovery Sequence (dSIR), which is used to image very small changes in T
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 T
from normal in other tissues. In the T
domain, we describe the divided echo subtraction (dES) sequence that is used to image musculoskeletal tissues with a very short T
*. 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.
Our study methodology is motivated from three disparate needs: one, imaging studies have existed in silo and study organs but not across organ systems; two, there are gaps in our understanding of ...paediatric structure and function; three, lack of representative data in New Zealand. Our research aims to address these issues in part, through the combination of magnetic resonance imaging, advanced image processing algorithms and computational modelling. Our study demonstrated the need to take an organ-system approach and scan multiple organs on the same child. We have pilot tested an imaging protocol to be minimally disruptive to the children and demonstrated state-of-the-art image processing and personalized computational models using the imaging data. Our imaging protocol spans brain, lungs, heart, muscle, bones, abdominal and vascular systems. Our initial set of results demonstrated child-specific measurements on one dataset. This work is novel and interesting as we have run multiple computational physiology workflows to generate personalized computational models. Our proposed work is the first step towards achieving the integration of imaging and modelling improving our understanding of the human body in paediatric health and disease.
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. T
-weighted spin echo (T
-wSE) and/or T
-Fluid Attenuated Inversion Recovery (T
-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.
Two cases of DPHL imaged with MRI nine months and two years after probable hypoxic episodes are described. No abnormalities were seen on the T
-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 T
. The clinical findings in both cases were of cognitive impairment without Parkinsonism or akinetic mutism.
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.
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.
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 Tsub.1 or Tsub.2 weighting over a small range of tissues with specific Tsub.1 and Tsub.2 values. In the Tsub.1 domain, we describe the implementation of the divided Subtracted Inversion Recovery Sequence (dSIR), which is used to image very small changes in Tsub.1 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 Tsub.1 from normal in other tissues. In the Tsub.2 domain, we describe the divided echo subtraction (dES) sequence that is used to image musculoskeletal tissues with a very short Tsub.2*. 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.
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. Tsub.2-weighted spin echo (Tsub.2-wSE) and/or Tsub.2-Fluid Attenuated Inversion Recovery (Tsub.2-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 Tsub.2-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 Tsub.1. 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.
Averaging is commonly used for data reduction/aggregation to analyse high-dimensional MRI data, but this often leads to information loss. To address this issue, we developed a novel technique that ...integrates diffusion tensor metrics along the whole volume of the fibre bundle using a 3D mesh-morphing technique coupled with principal component analysis for delineating case and control groups. Brain diffusion tensor MRI scans of high school rugby union players (
= 30, age 16-18) were acquired on a 3 T MRI before and after the sports season. A non-contact sport athlete cohort with matching demographics (
= 12) was also scanned. The utility of the new method in detecting differences in diffusion tensor metrics of the right corticospinal tract between contact and non-contact sport athletes was explored. The first step was to run automated tractography on each subject's native space. A template model of the right corticospinal tract was generated and morphed into each subject's native shape and space, matching individual geometry and diffusion metric distributions with minimal information loss. The common dimension of the 20 480 diffusion metrics allowed further data aggregation using principal component analysis to cluster the case and control groups as well as visualization of diffusion metric statistics (mean, ±2 SD). Our approach of analysing the whole volume of white matter tracts led to a clear delineation between the rugby and control cohort, which was not possible with the traditional averaging method. Moreover, our approach accounts for the individual subject's variations in diffusion tensor metrics to visualize group differences in quantitative MR data. This approach may benefit future prediction models based on other quantitative MRI methods.
This paper updates and extends three previous papers on tissue property filters (TP-filters), Multiplied, Added, Divided and/or Subtracted Inversion Recovery (MASTIR) pulse sequences and synergistic ...contrast MRI (scMRI). It does this by firstly adding the central contrast theorem (CCT) to TP-filters, secondly including division with MASTIR sequences to make them Multiplied, Added, Subtracted and/or Divided IR (MASDIR) sequences, and thirdly incorporating division into the image processing needed for scMR to increase synergistic T
contrast. These updated concepts are then used to explain and improve contrast at tissue boundaries, as well as to develop imaging regimes to detect and monitor small changes to the brain over time and quantify T
. The CCT is in two parts: the first part states that contrast produced by each TP is the product of the change in TP multiplied by the TP sequence weighting which is the first partial derivative of the TP-filter. The second part states that the overall fractional contrast is the algebraic sum of the fractional contrasts produced by each of the TPs. Subtraction of two IR sequences alone about doubles contrast relative to a conventional single IR sequence. Division of this subtraction can amplify contrast 5-15 times compared with conventional IR sequences. Dividing sequences can be problematic in areas where the signal is zero but this is avoided by dividing the difference in signal of two magnitude reconstructed IR sequences by the sum of their signals. The basis for the production of high contrast, high spatial resolution boundaries at white-gray matter junctions, between cerebral cortex and cerebrospinal fluid (CSF) and at other sites with subtracted IR (SIR) and divided subtracted IR (dSIR) sequences is explained and examples are shown. A key concept is the tissue fraction f, which is the proportion of a tissue in a mixture of two tissues within a voxel. Contrast at boundaries is a function of the partial derivative of the TP-filter, the partial derivative of the relevant TP with respect to f, and the partial derivative of f with respect to distance, x. Location of tissue boundaries is important for segmentation and is helpful in determining if inversion times have been chosen correctly. In small change regimes, the high sensitivity to small changes in T
provided by dSIR images, together with the high definition boundaries, afford mechanisms for detecting small changes due to contrast agents, disease, perfusion and other causes. 3D isotropic rigid body registration provides a technique for following these changes over time in serial studies. Images showing high lesion contrast, high definition tissue and fluid boundaries, and the detection of small changes are included. T1 maps can be created by linearly scaling dSIR images.
