Divided subtracted inversion recovery (dSIR) images show abnormal changes in the white matter of the brain in patients with mild traumatic brain injury (mTBI) due to an increase in the apparent T1 compared to normal controls. The present study aims to understand the origin of the T1 difference in terms of incidental magnetization transfer (MT). Results show that white matter in normal controls has dSIR signal (T1), attributable to MT, while patients with mTBI exhibit little or no reduction. The study identifies a plausible mechanism for the dSIR signal differences. This may lead to more effective magnetic resonance imaging (MRI) methods for detecting mTBI and other conditions affecting the brain.

Recent interest in musculoskeletal connective tissues like tendons, aponeurosis, and deep fascia has led to a greater focus on in vivo medical imaging, particularly MRI. Given the rapid T2* decay of collagenous tissues, advanced ultra-short echo time (UTE) MRI sequences have proven useful in generating high-signal images of these tissues. To further these advances, we discuss the integration of UTE with Diffusion Tensor Imaging (DTI) and explore image processing techniques to enhance the localization, labeling, and modeling of connective tissues. These techniques are especially valuable for extracting features from thin tissues that may be difficult to distinguish. We present data from lower leg scans of 30 healthy subjects using a non-Cartesian MRI sequence to acquire axial 2D images to segment skeletal muscle and connective tissue. DTI helped differentiate aponeurosis from deep fascia by analyzing muscle fiber orientations. The dual echo imaging methods yielded high-resolution images of deep fascia, where in-plane spatial resolutions were between 0.3 × 0.3 mm to 0.5 × 0.5 mm with a slice thickness of 3–5 mm. Techniques such as K-Means clustering, FFT edge detection, and region-specific scaling were most effective in enhancing images of deep fascia, aponeurosis, and tendon to enable high-fidelity modeling of these tissues.

Magnetic resonance imaging (MRI) techniques have recently been developed for obtaining high T1 contrast images using inversion recovery (IR) images at two inversion times (TIs) rather than a single TI. They use simple mathematical operations - multiplication, addition, subtraction, division - to create images not attainable by conventional IR. The present study describes a novel two-point IR technique formed by the subtraction of log images. Results show it has a near-linear response to T1 between the nullpoints that peaks sharply at the null- points. This produces a bright isoT1 contour at interfaces between tissues where partial volume mixing generates specific T1s. This can provide anatomical information in areas where the signal is not well-differentiated on conventional images.

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). 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. 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. 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. 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.

The cartilaginous endplate (CEP) plays a pivotal role in facilitating the supply of nutrients and, transport of metabolic waste, as well as providing mechanical support for the intervertebral disc (IVD). Recent technological advances have led to a surge in MR imaging studies focused on the CEP. This article describes the anatomy and functions of the CEP as well as MRI techniques for both qualitative and quantitative assessment of the CEP. Effective CEP MR imaging sequences require two key features: high spatial resolution and relatively short echo time. High spatial resolution spoiled gradient echo (SPGR) and ultrashort echo time (UTE) sequences, fulfilling these requirements, are the basis for most of the sequences employed in CEP imaging. This article reviews existing sequences for qualitative CEP imaging, such as the fat-suppressed SPGR and UTE, dual-echo subtraction UTE, inversion recovery prepared and fat-suppressed UTE, and dual inversion recovery prepared UTE sequences. These sequences are employed together with other techniques for quantitative CEP imaging, including measurements of T2*, T2, T1, T1ρ, magnetization transfer, perfusion, and diffusion tensor parameters. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

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.

Background:Myelin water imaging (MWI) is a myelin-specific technique, which has great potential for the assessment of demyelination and remyelination. This study develops a new MWI method, which employs a short repetition time adiabatic inversion recovery (STAIR) technique in combination with a commonly used fast spin echo (FSE) sequence and provides quantification of myelin water (MW) fractions. Method:Whole-brain MWI was performed using the short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) technique on eight healthy volunteers (mean age: 38±14 years, four-males) and seven patients with multiple sclerosis (MS) (mean age: 53.7±8.7 years, two-males) on a 3T clinical magnetic resonance imaging scanner. To facilitate the quantification of apparent myelin water fraction (aMWF), a proton density-weighted FSE was also used during the scans to allow total water imaging. The aMWF measurements of MS lesions and normal-appearing white matter (NAWM) regions in MS patients were compared with those measured in normal white matter (NWM) regions in healthy volunteers. Both the analysis of variance (ANOVA) test and paired comparison were performed for the comparison. Results:The MW in the whole-brain was selectively imaged and quantified using the STAIR-FSE technique in all participants. MS lesions showed much lower signal intensities than NAWM in the STAIR-FSE images. ANOVA analysis revealed a significant difference in the aMWF measurements between the three groups. Moreover, the aMWF measurements in MS lesions were significantly lower than those in both NWM of healthy volunteers and NAWM of MS patients. Lower aMWF measurements in NAWM were also found in comparison with those in NWM. Conclusions:The STAIR-FSE technique is capable of measuring aMWF values for the indirect detection of myelin loss in MS, thus facilitating clinical translation of whole brain MWI and quantification, which show great potential for the detection and evaluation of changes in myelin in the brain of patients with MS for future larger cohort studies.

PURPOSE:Balanced steady-state free precession (bSSFP) imaging is susceptible to outflow effects where excited spins leaving the slice as part of the blood stream are misprojected back onto the imaging plane. Previous work proposed using slice-encoding steps to localize these outflow effects from corrupting the target slice, at the expense of prolonged scan time. This present study extends this idea by proposing a means of significantly reducing most of the outflowing signal from the imaged slice using a coil localization method that acquires a slice-encoded calibration scan in addition to the 2D data, without being nearly as time-demanding as our previous method. This coil localization method is titled UNfolding Coil Localized Errors from an imperfect slice profile using a Structured Autocalibration Matrix (UNCLE SAM). METHODS:Retrospective and prospective evaluations were carried out. Both featured a 2D acquisition and a separate slice-encoded calibration of the center in-plane k -space lines across all desired slice-encoding steps. RESULTS:Retrospective results featured a slice-by-slice comparison of the slice-encoded images with UNCLE SAM. UNCLE SAM's subtraction from the slice-encoded image was compared with a subtraction from the flow-corrupted 2D image, to demonstrate UNCLE SAM's capability to unfold outflowing spins. UNCLE SAM's comparison with slice encoding showed that UNCLE SAM was able to unfold up to 74% of what slice encoding achieved. Prospective results showed significant reduction in outflow effects with only a marginal increase in scan time from the 2D acquisition. CONCLUSIONS:We developed a method that effectively unfolds most outflowing spins from corrupting the target slice and does not require the explicit use of slice-encoding gradients. This development offers a method to reduce most outflow effects from the target slice within a clinically feasible scan duration compared with the fully sampled slice-encoding technique.

In this study, we describe a comprehensive 3D magnetic resonance imaging (MRI) protocol designed to assess major tissue and fluid components in the brain. The protocol comprises four different sequences: 1) magnetization transfer prepared Cones (MT-Cones) for two-pool MT modeling to quantify macromolecular content; 2) short-TR adiabatic inversion-recovery prepared Cones (STAIR-Cones) for myelin water imaging; 3) proton-density weighted Cones (PDw-Cones) for total water imaging; and 4) highly T2 weighted Cones (T2w-Cones) for free water imaging. By integrating these techniques, we successfully mapped key brain components—namely macromolecules, myelin water, intra/extracellular water, and free water—in ten healthy volunteers and five patients with multiple sclerosis (MS) using a 3T clinical scanner. Brain macromolecular proton fraction (MMPF), myelin water proton fraction (MWPF), intra/extracellular water proton fraction (IEWPF), and free water proton fraction (FWPF) values were generated in white matter (WM), grey matter (GM), and MS lesions. Excellent repeatability of the protocol was demonstrated with high intra-class correlation coefficient (ICC) values. In MS patients, the MMPF and MWPF values of the lesions and normal-appearing WM (NAWM) were significantly lower than those in normal WM (NWM) in healthy volunteers. Moreover, we observed significantly higher FWPF values in MS lesions compared to those in NWM and NAWM regions. This study demonstrates the capability of our technique to volumetrically map major brain components. The technique may have particular value in providing a comprehensive assessment of neuroinflammatory and neurodegenerative diseases of the brain.

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.

PURPOSE:To develop a new sequence to simultaneously acquire Cartesian sodium (23Na) MRI and accelerated Cartesian single (SQ) and triple quantum (TQ) sodium MRI of in vivo human brain at 7 T by leveraging two dedicated low-rank reconstruction frameworks. THEORY AND METHODS:The Double Half-Echo technique enables short echo time Cartesian 23Na MRI and acquires two k-space halves, reconstructed by a low-rank coupling constraint. Additionally, three-dimensional (3D) 23Na Multi-Quantum Coherences (MQC) MRI requires multi-echo sampling paired with phase-cycling, exhibiting a redundant multidimensional space. Simultaneous Autocalibrating and k-Space Estimation (SAKE) were used to reconstruct highly undersampled 23Na MQC MRI. Reconstruction performance was assessed against five-dimensional (5D) CS, evaluating structural similarity index (SSIM), root mean squared error (RMSE), signal-to-noise ratio (SNR), and quantification of tissue sodium concentration and TQ/SQ ratio in silico, in vitro, and in vivo. RESULTS:The proposed sequence enabled the simultaneous acquisition of fully sampled 23Na MRI while leveraging prospective undersampling for 23Na MQC MRI. SAKE improved TQ image reconstruction regarding SSIM by 6% and reduced RMSE by 35% compared to 5D CS in vivo. Thanks to prospective undersampling, the spatial resolution of 23Na MQC MRI was enhanced from 8 × 8 × 15 $$ 8\times 8\times 15 $$ mm3 to 8 × 8 × 8 $$ 8\times 8\times 8 $$ mm3 while reducing acquisition time from 2 × 31 $$ 2\times 31 $$ min to 2 × 23 $$ 2\times 23 $$ min. CONCLUSION:The proposed sequence, coupled with low-rank reconstructions, provides an efficient framework for comprehensive whole-brain sodium MRI, combining TSC, T2*, and TQ/SQ ratio estimations. Additionally, low-rank matrix completion enables the reconstruction of highly undersampled 23Na MQC MRI, allowing for accelerated acquisition or enhanced spatial resolution.

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.

The divided subtracted inversion recovery (dSIR) is a high T-1 contrast technique that shows changes in white matter in patients with traumatic brain injury and hypoxic injury. The changes can be explained by small differences in T-1; however, to date, there has been no independent validation of the technique using a standard reference. The present study develops the theory of the dSIR signal and performs validation using the NIST/ISMRM T-1 phantom. Non-idealities are explored, including the influence of noise bias and finite repetition time (TR), which leads to the introduction of an optimally efficient TR for inversion recovery acquisitions. Results show excellent agreement with theoretical calculations.

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.

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T-1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T-1 by up to 15 times compared to conventional T-1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T-1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T-2-weighted spin echo (T-2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T-1 or T-2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T-1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T-1 maps. There is a nearly linear relationship between signal and T-1 in the middle domain (mD) of the two sequences which includes T(1)s between the nulling T(1)s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T-1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T-1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T-2-wSE and T-2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T-1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T-1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.