Longitudinal MR Imaging Research Articles

A Transverse and Longitudinal MR Imaging Voxel-Based Morphometry Study in Patients with Primary Cervical Dystonia

Findings of standard MR imaging examinations are usually normal in primary CD. These findings are now increasingly challenged by studies using advanced neuroimaging techniques detecting abnormalities in brain areas that may be functionally involved in the pathophysiology of CD. Our purpose was to evaluate GM volumes in patients with CD at baseline and 5 years later. We enrolled 19 patients (F/M = 15:4, mean age = 53.2 + 11.2 years), 12 of whom were studied at baseline and again approximately 5 years later. Twenty-eight healthy volunteers acted as controls (F/M = 17:11, mean age = 47.5 + 15.6 years). The subjects were imaged with a 1.5T scanner by using a 3D T1-weighted sequence on 150 contiguous axial 1-mm-thick sections to apply VBM. At entry, VBM analysis disclosed significantly lower GM volumes in the left caudate head and putamen and in the premotor and primary sensorimotor cortices bilaterally in patients than in controls. No correlation was found between decreased GM volumes and patient age, severity of dystonia, or disease duration. At the 5-year follow-up, GM volumes in the left primary sensorimotor cortex in patients had decreased significantly from baseline. The findings obtained at entry and after a 5-year follow-up consistently showed decreased caudate, putamen, and sensorimotor cortex GM volumes in patients with CD, and they probably play a pathophysiologic role in CD.

Validation of an algorithm for the nonrigid registration of longitudinal breast MR images using realistic phantoms

The authors present a method to validate coregistration of breast magnetic resonance images obtained at multiple time points during the course of treatment. In performing sequential registration of breast images, the effects of patient repositioning, as well as possible changes in tumor shape and volume, must be considered. The authors accomplish this by extending the adaptive bases algorithm (ABA) to include a tumor-volume preserving constraint in the cost function. In this study, the authors evaluate this approach using a novel validation method that simulates not only the bulk deformation associated with breast MR images obtained at different time points, but also the reduction in tumor volume typically observed as a response to neoadjuvant chemotherapy. For each of the six patients, high-resolution 3D contrast enhanced T1-weighted images were obtained before treatment, after one cycle of chemotherapy and at the conclusion of chemotherapy. To evaluate the effects of decreasing tumor size during the course of therapy, simulations were run in which the tumor in the original images was contracted by 25%, 50%, 75%, and 95%, respectively. The contracted area was then filled using texture from local healthy appearing tissue. Next, to simulate the post-treatment data, the simulated (i.e., contracted tumor) images were coregistered to the experimentally measured post-treatment images using a surface registration. By comparing the deformations generated by the constrained and unconstrained version of ABA, the authors assessed the accuracy of the registration algorithms. The authors also applied the two algorithms on experimental data to study the tumor volume changes, the value of the constraint, and the smoothness of transformations. For the six patient data sets, the average voxel shift error (mean +/- standard deviation) for the ABA with constraint was 0.45 +/- 0.37, 0.97 +/- 0.83, 1.43 +/- 0.96, and 1.80 +/- 1.17 mm for the 25%, 50%, 75%, and 95% contraction simulations, respectively. In comparison, the average voxel shift error for the unconstrained ABA was 0.46 +/- 0.29, 1.13 +/- 1.17, 2.40 +/- 2.04, and 3.53 +/- 2.89 mm, respectively. These voxel shift errors translate into compression of the tumor volume: The ABA with constraint returned volumetric errors of 2.70 +/- 4.08%, 7.31 +/- 4.52%, 9.28 +/- 5.55%, and 13.19 +/- 6.73% for the 25%, 50%, 75%, and 95% contraction simulations, respectively, whereas the unconstrained ABA returned volumetric errors of 4.00 +/- 4.46%, 9.93 +/- 4.83%, 19.78 +/- 5.657%, and 29.75 +/- 15.18%. The ABA with constraint yields a smaller mean shift error, as well as a smaller volume error (p = 0.031 25 for the 75% and 95% contractions), than the unconstrained ABA for the simulated sets. Visual and quantitative assessments on experimental data also indicate a good performance of the proposed algorithm. The ABA with constraint can successfully register breast MR images acquired at different time points with reasonable error. To the best of the authors' knowledge, this is the first report of an attempt to quantitatively assess in both phantoms and a set of patients the accuracy of a registration algorithm for this purpose.

Onset and Progression of Pathologic Atrophy in Huntington Disease: A Longitudinal MR Imaging Study

Longitudinal MR imaging measures provide an opportunity to track progression in HD before the emergence of clinical symptoms. This may prove useful in assessing disease-modifying treatments. We investigated how caudate and global volumes change as HD progresses from premanifest to early disease. Forty HD gene-positive individuals and 19 controls underwent serial volumetric MR imaging (baseline, 12 and 27 months; 2 or 3 scans per person). At baseline, 3 patients with HD were premanifest but developed overt motor features during the study, and 37 had early HD. All had dates of motor onset recorded. Caudates, lateral ventricles, and TIVs were measured using semiautomated procedures. Linear mixed models were used to investigate differences between HD and controls in relation to motor onset, controlling for TIV, sex, and age. Extrapolating backwards in time, we found that differences in caudate and ventricular volumes between patients with HD and controls were evident 14 and 5 years, respectively, before motor onset (P < .05). At onset, caudate volume was 2.58 mL smaller than that in controls (P < .0001); ventricular volume was 9.27 mL larger (P < .0001). HD caudate atrophy rates were linear, showed low variability between subjects, and were approximately 10-fold higher than those in controls (P < .001). HD ventricular enlargement rates were variable between subjects, were approximately 4-fold higher than those in controls at onset (P < .001), and accelerated with disease duration (P = .02). We provide evidence of acceleration of global atrophy in HD with disproportionate caudate involvement. Both caudate and global measures may be of use as early markers of HD pathology.

Deformation invariant attribute vector for deformable registration of longitudinal brain MR images

This paper presents a novel approach to define deformation invariant attribute vector (DIAV) for each voxel in 3D brain image for the purpose of anatomic correspondence detection. The DIAV method is validated by using synthesized deformation in 3D brain MRI images. Both theoretic analysis and experimental studies demonstrate that the proposed DIAV is invariant to general nonlinear deformation. Moreover, our experimental results show that the DIAV is able to capture rich anatomic information around the voxels and exhibit strong discriminative ability. The DIAV has been integrated into a deformable registration algorithm for longitudinal brain MR images, and the results on both simulated and real brain images are provided to demonstrate the good performance of the proposed registration algorithm based on matching of DIAVs.

60. Male brain shrinks faster than female brain – A longitudinal brain MR image analysis

60. Male brain shrinks faster than female brain – A longitudinal brain MR image analysis

The Rare Association of Moyamoya Disease and Cerebral Arteriovenous Malformations: a Case Report

A 36-year-old man was diagnosed with a right temporal lobe grade II cerebral arteriovenous malformation (cAVM) and was treated with radiosurgery. At nine months after the cAVM radiosurgery, the patient began to develop bilateral focal narrowing at the M1 segments of the bilateral middle cerebral arteries. The narrowing progressively deteriorated as was demonstrated on longitudinal serial follow-up MR imaging. X-ray angiography performed at 51 months after radiosurgery confirmed that the cAVM was cured and a diagnosis of moyamoya disease. To the best of our knowledge, this is the first case of cAVM-associated moyamoya disease that developed after radiosurgery. Given the chronological sequence of disease development and radiation dose distribution of radiosurgery, it is proposed that humoral or unknown predisposing factors, rather than direct radiation effects, are the cause of moyamoya disease associated with cAVM.

Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils

Measures of structural brain change based on longitudinal MR imaging are increasingly important but can be degraded by intensity non-uniformity. This non-uniformity can be more pronounced at higher field strengths, or when using multichannel receiver coils. We assessed the ability of the non-parametric non-uniform intensity normalization (N3) technique to correct non-uniformity in 72 volumetric brain MR scans from the preparatory phase of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Normal elderly subjects ( n = 18) were scanned on different 3-T scanners with a multichannel phased array receiver coil at baseline, using magnetization prepared rapid gradient echo (MP-RAGE) and spoiled gradient echo (SPGR) pulse sequences, and again 2 weeks later. When applying N3, we used five brain masks of varying accuracy and four spline smoothing distances ( d = 50, 100, 150 and 200 mm) to ascertain which combination of parameters optimally reduces the non-uniformity. We used the normalized white matter intensity variance (standard deviation/mean) to ascertain quantitatively the correction for a single scan; we used the variance of the normalized difference image to assess quantitatively the consistency of the correction over time from registered scan pairs. Our results showed statistically significant ( p < 0.01) improvement in uniformity for individual scans and reduction in the normalized difference image variance when using masks that identified distinct brain tissue classes, and when using smaller spline smoothing distances (e.g., 50–100 mm) for both MP-RAGE and SPGR pulse sequences. These optimized settings may assist future large-scale studies where 3-T scanners and phased array receiver coils are used, such as ADNI, so that intensity non-uniformity does not influence the power of MR imaging to detect disease progression and the factors that influence it.

Assessment of brain growth in early childhood using deformation-based morphometry

We present methods for the quantitative analysis of brain growth based on the registration of longitudinal MR image data with the use of Jacobian determinant maps to characterise neuroanatomical changes. The individual anatomies, growth maps and tissue classes are also spatially normalised in an ‘average space’ and aggregated to provide atlases for the population at each timepoint. The average space representation is obtained using the average intersubject transformation within each timepoint. In an exemplar study, this approach is used to assess brain development in 25 infants between 1 and 2 years, and we show consistency in growth estimates between registration and segmentation approaches.

Sci‐Fri PM Imaging‐12: Multimodal Contrast Agent for Combined CT and MR Imaging

Interest in the area of multimodality imaging has also been prompted by the realization that such techniques offer much more sophisticated characterization of the morphology and physiology of tissues and organs, and that confidence gained in the accurate correspondence or registration of different modalities greatly enhances their value. This study is aimed to provide a contrast agent based approach to combine information obtained in CT and MR. Specifically, a liposome‐based dual modality contrast agent co‐encapsulating iohexol, an iodine‐based CT contrast agent, and gadoteridol, a gadolinium‐based MR contrast agent, was developed and characterized. Previously, our group characterized the in vitro physico‐chemical properties of this liposome‐based contrast agent. In this study, CT and MR‐based assessments of the in vivo stability of the liposome‐based contrast agent was conducted in a rabbit model. Visual contrast enhancement and measurable signal increases produced by the presence of the contrast agent carrying liposomes was induced in various organ systems (i.e. heart and blood vessels, liver, spleen, kidney and intestines) in both imaging systems over a 7‐day period. The blood circulation half‐life of the present liposome formulation in rabbits was found to be 45.4 ± 2.5 hours. The simultaneous signal enhancement seen in both CT and MR, and the long circulation life of this liposome‐based contrast agent makes it attractive for use in applications such as longitudinal blood pool imaging, feature‐based CT and MR image registration, and imaging‐based tracking of liposomal therapeutics.

Correction of differential intensity inhomogeneity in longitudinal MR images

Longitudinal MR imaging is increasingly being used to measure cerebral atrophy progression in dementia and other neurological disorders. Differences in intensity inhomogeneity between serial scans can confound these measurements. This differential bias also distorts nonlinear registration and makes both manual and automated segmentation of tissue type less reliable. A technique is described for the correction of this differential bias that makes no assumptions about signal distribution, bias field or signal homogeneity. Instead, the bias field calculation is performed on the basis that the remaining structure in the difference image of registered serial scans has small-scale structure. The differential bias field is of much larger scale and can thus be obtained by applying an appropriate filter to the difference image. The serial scan pair is then corrected for the differential bias field and atrophy measurement can be performed on the corrected scan pair. Application of a known, simulated bias field to real serial MR images was shown to alter atrophy measurements significantly. The differential correction method recovered the applied differential bias field and thereby improved atrophy measurements. This method was then applied to serial imaging in patients with dementia using a set of serial scan pairs with visually identified, significant differential bias and a set of scan pairs with negligible differential bias. Differential bias correction specifically reduced the variance of the atrophy measure significantly for the scans with significant differential bias.

Thoracic spine disc-related abnormalities: longitudinal MR imaging assessment.

To describe and characterize the temporal changes in disc-related disorders of the thoracic spine using MR imaging. A retrospective longitudinal cohort study was carried out of 40 patients with two sequential thoracic spine MR images at variable intervals. The images were assessed for baseline presence of, new incidence of and changes in disc herniation, degenerative disc disease, endplate marrow signal alteration and Schmorl nodes. The range of follow-up was 4-149 weeks. Baseline presence was: disc herniation, 10% (49/480); degenerative disc disease, 14% (66/480); endplate marrow signal alteration, 2.3% (11/480); Schmorl nodes 9.6% (46/480). Most pre-existing lesions tended to remain unchanged. Herniations showed the most change, tending to improve in 27%. New incidence was: disc herniation, 1.5% (7/480), degenerative disc disease, 2% (10/480); endplate marrow signal alteration, 1.6% (8/480); Schmorl nodes, 2.1% (10/480). Disc degeneration was first visible at an 11-week interval and once established almost never changed over many weeks to months. Endplate signal alterations (Modic changes) were uncommon. Schmorl nodes show no change from baseline for up to 2 1/2 years. All findings predominated in the lower intervertebral levels from T6 to T10. The most prevalent thoracic spine disc-related findings are degeneration and herniation. Disc herniations predominate in the lower segments and are a dynamic phenomenon. Disc degeneration can be rapidly evolving but tends to remain unchanged after occurrence. Endplate marrow signal changes were an uncommon manifestation of thoracic disc disease. Schmorl nodes showed the least change over time.

Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced dose craniospinal irradiation☆

Medulloblastoma is the most common malignant brain tumor in children, and approximately seventy percent of average-risk patients will achieve long-term survival. Craniospinal irradiation (CSI), combined with chemotherapy and surgery, is currently the mainstay of treatment but places children who survive at risk for serious neurocognitive sequelae. These sequelae are intensified with a younger age at treatment, greater elapsed time following treatment, and an increased radiation dose. Many newer treatment approaches have attempted to address this problem by reducing the dose of the CSI component of radiation therapy while maintaining the current survival rates. This study evaluates longitudinal MR imaging during therapy to assess the impact of the two CSI doses (conventional [36 Gy] and reduced [23.4 Gy]) on normal appearing white matter volumes (NAWMV) evaluated in a single index slice. Twenty-six children and young adults at least three years of age enrolled on an institutional protocol for newly diagnosed, previously untreated primary medulloblastoma had at least four MR examinations over a minimum nine month period following CSI. These serial volumes were evaluated as a function of time since CSI in three analyses: 1) all subjects, 2) subjects stratified by age at CSI, and 3) subjects stratified by CSI dose. The first analysis demonstrated that medulloblastoma patients treated with CSI have a significant loss of NAWMV in contradistiction to normally expected maturation. Stratifying the patients by age at CSI found no significant differences in the rate of NAWMV loss. The final analysis stratified the patients by CSI dose and revealed that the rate of NAWMV loss was 23% slower in children receiving reduced-dose. Serial quantitative MR measures of NAWMV may provide a neuroanatomical substrate for assessing functional impact of CSI on normal brain function following treatment for medulloblastoma.

Longitudinal MR imaging and proton MR spectroscopy in herpes simplex encephalitis

Longitudinal MR imaging and proton MR spectroscopy were performed in an 11 year-old female case of herpes simplex encephalitis with a complete recovery. On MR imaging, the white matter lesions, which could be seen in the subacute stage, but not in the acute or chronic stage, might represent edema due to postinfectious neuroallergic phenomena. Proton MR spectroscopy revealed marked reduction of the NAA/Cr ratio in the chronic stage, which increased gradually to within normal range in a year.