The Current State of Susceptibility-Weighted Imaging and Quantitative Susceptibility Mapping in Head Trauma.

Susceptibility-weighted imaging (SWI) is a MR imaging technique suited to detect structural and microstructural abnormalities in traumatic brain injury (TBI). This review article provide an insight in to the physics principles of SWI and its clinical application in unraveling the complex interaction of the biophysical mechanisms of head injury. Literature evidences support SWI as the most ideal sequence in detection of microbleeds, which is the "tip of the iceberg" biomarker of microvascular injuries. The review also detailed the emerging advance techniques of Quantitative susceptibility mapping (QSM) and artificial intelligence offer the ability to detect and follow the evolution of microbleeds in patient with chronic TBI. These new techniques offers a unique insight into the acute and chronic state of TBI.

An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis.

The etiology of multiple sclerosis (MS) is currently understood to be autoimmune. However, there is a long history and growing evidence for disrupted vasculature and flow within the disease pathology. A broad review of the literature related to vascular effects in MS revealed a suggestive role for abnormal flow in the medullary vein system. Evidence for venous involvement in multiple sclerosis dates back to the early pathological work by Charcot and Bourneville, in the mid-nineteenth century. Pioneering work by Adams in the 1980s demonstrated vasculitis within the walls of veins and venules proximal to active MS lesions. And more recently, magnetic resonance imaging (MRI) has been used to show manifestations of the central vein as a precursor to the development of new MS lesions, and high-resolution MRI using Ferumoxytol has been used to reveal the microvasculature that has previously only been demonstrated in cadaver brains. Both approaches may shed new light into the structural changes occurring in MS lesions. The material covered in this review shows that multiple pathophysiological events may occur sequentially, in parallel, or in a vicious circle which include: endothelial damage, venous collagenosis and fibrin deposition, loss of vessel compliance, venous hypertension, perfusion reduction followed by ischemia, medullary vein dilation and local vascular remodeling. We come to the conclusion that a potential source of MS lesions is due to locally disrupted flow which in turn leads to remodeling of the medullary veins followed by endothelial damage with the subsequent escape of glial cells, cytokines, etc. These ultimately lead to the cascade of inflammatory and demyelinating events which ensue in the course of the disease.

Imaging iron and neuromelanin simultaneously using a single 3D gradient echo magnetization transfer sequence: Combining neuromelanin, iron and the nigrosome-1 sign as complementary imaging biomarkers in early stage Parkinson's disease.

Diagnosing early stage Parkinson's disease (PD) is still a clinical challenge. Previous studies using iron, neuromelanin (NM) or the Nigrosome-1 (N1) sign in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. Our goal in this study was to extract the NM complex volume, iron content and volume representing the entire SN, and the N1 sign as potential complementary imaging biomarkers using a single 3D magnetization transfer contrast (MTC) gradient echo sequence and to evaluate their diagnostic performance and clinical correlations in early stage PD. A total of 40 early stage idiopathic PD subjects and 40 age- and sex-matched healthy controls (HCs) were imaged at 3T. NM boundaries (representing the SN pars compacta (SNpc) and parabrachial pigmented nucleus) and iron boundaries representing the total SN (SNpc and SN pars reticulata) were determined semi-automatically using a dynamic programming (DP) boundary detection algorithm. Receiver operating characteristic analyses were performed to evaluate the utility of these imaging biomarkers in diagnosing early stage PD. A correlation analysis was used to study the relationship between these imaging measures and the clinical scales. We also introduced the concept of NM and total iron overlap volumes to demonstrate the loss of NM relative to the iron containing SN. Furthermore, all 80 cases were evaluated for the N1 sign independently. The NM and SN volumes were lower while the iron content was higher in the SN for PD subjects compared to HCs. Interestingly, the PD subjects with bilateral loss of the N1 sign had the highest iron content. The area under the curve (AUC) values for the average of both hemispheres for single measures were: .960 for NM complex volume; .788 for total SN volume; .740 for SN iron content and .891 for the N1 sign. Combining NM complex volume with each of the following measures through binary logistic regression led to AUC values for the averaged right and left sides of: .976 for total iron content; .969 for total SN volume, .965 for overlap volume and .983 for the N1 sign. We found a negative correlation between SN volume and UPDRS-III (R2 = .22, p = .002). While the N1 sign performed well, it does not contain any information about iron content or NM quantitatively, therefore, marrying this sign with the NM and iron measures provides a better physiological explanation of what is happening when the N1 sign disappears in PD subjects. In summary, the combination of NM complex volume, SN volume, iron content and the N1 sign as derived from a single MTC sequence provides complementary information for understanding and diagnosing early stage PD.

A Comparison of Magnetic Resonance Imaging Methods to Assess Multiple Sclerosis Lesions: Implications for Patient Characterization and Clinical Trial Design.

Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 weighted imaging (T1WI, T2WI), T2 fluid attenuated inversion recovery (FLAIR), magnetization transfer, myelin water fraction, diffusion tensor imaging (DTI), phase-sensitive inversion recovery and susceptibility weighted imaging (SWI), but no study has combined all of these modalities into a single well-controlled investigation. The goals of this study were to: compare different MRI measures for lesion visualization and quantification; evaluate the repeatability of various imaging methods in healthy controls; compare quantitative susceptibility mapping (QSM) with myelin water fraction; measure short-term longitudinal changes in the white matter of MS patients and map out the tissue properties of the white matter hyperintensities using STAGE (strategically acquired gradient echo imaging). Additionally, the outcomes of this study were anticipated to aid in the choice of an efficient imaging protocol reducing redundancy of information and alleviating patient burden. Of all the sequences used, T2 FLAIR and T2WI showed the most lesions. To differentiate the putative demyelinating lesions from inflammatory lesions, the fusion of SWI and T2 FLAIR was used. Our study suggests that a practical and efficient imaging protocol combining T2 FLAIR, T1WI and STAGE (with SWI and QSM) can be used to rapidly image MS patients to both find lesions and study the demyelinating and inflammatory characteristics of the lesions.

Longitudinal Magnetic Resonance Imaging of Cerebral Microbleeds in Multiple Sclerosis Patients.

We hypothesized that cerebral microbleeds (CMBs) in multiple sclerosis (MS) patients will be detected with higher prevalence compared to healthy controls (HC) and that quantitative susceptibility mapping (QSM) will help remove false positives seen in susceptibility weighted imaging (SWI). A cohort of 100 relapsing remitting MS subjects scanned at 3T were used to validate a set of CMB detection guidelines specifically using QSM. A second longitudinal cohort of 112 MS and 25 HCs, also acquired at 3T, was reviewed across two time points. Both cohorts were imaged with SWI and fluid attenuated inversion recovery. Fourteen subjects in the first cohort (14%, 95% CI 8-21%) and twenty-one subjects in the second cohort (18.7%, 95% CI 11-27%) had at least one CMB. The combined information from SWI and QSM allowed us to discern stable CMBs and new CMBs from potential mimics and evaluate changes over time. The longitudinal results demonstrated that longer disease duration increased the chance to develop new CMBs. Higher age was also associated with increased CMB prevalence for MS and HC. We observed that MS subjects developed new CMBs between time points, indicating the need for longitudinal quantitative imaging of CMBs.

Susceptibility and Volume Measures of the Mammillary Bodies Between Mild Cognitively Impaired Patients and Healthy Controls.

PURPOSE: To investigate the baseline values and differences for susceptibility and volume of the mammillary bodies between mild cognitively impaired (MCI) patients and healthy controls (HCs), and further explore their differences in relation to gender, MCI subtypes and apolipoprotein E (APOE) genotypes. METHODS: T1-weighted and multi-echo gradient echo imaging sequences were acquired on a 3T MR scanner to evaluate the T1W based volume and susceptibility differences in the mammillary body for 47 MCI and 47 HCs. T-tests were performed to compare volume and susceptibility between groups, and right and left hemispheres. Correlation analysis was used to relate the volume and mean susceptibility as a function of age in MCI and HC groups separately, and to investigate the relationship of susceptibility with the neuro-psychological scales in the MCI group. RESULTS: Susceptibility was found to be elevated within the right mammillary body in MCI patients compared to HCs (p < 0.05). There were no differences for the mammillary body volumes between the MCI and HC groups, although there was a reduction in volume with age for the MCI group (p = 0.007). Women showed decreased mammillary body volume compared to men in the HC group (p = 0.004). No significant differences were found in relation to MCI subtypes and APOE genotypes. No significant correlations were observed between mammillary body susceptibility with neuro-psychological scales. CONCLUSION: This work provides a quantitative baseline for both the volume and susceptibility of the mammillary body which can be used for future studies of cognitive impairment patients underlying the pathology of the Papez circuit.

Intracranial iron distribution and quantification in aceruloplasminemia: A case study.

OBJECTIVES: Aceruloplasminemia (ACP) is a rare autosomal recessive disorder characterized by intracranial and visceral iron overload. With R2*-based imaging or quantitative susceptibility mapping (QSM), it is feasible to measure iron in the brain quantitatively, although to date this has not yet been done for patients with ACP. The aim of this study was to provide quantitative iron measurements for each affected brain region in an ACP patient with the potential to do so in all future ACP patients. This may shed light on the link between brain iron metabolism and the territories affected by ceruloplasmin function. METHODS: We imaged a patient with ACP using a 3T magnetic resonance imaging scanner with a fifteen-channel head coil. We manually demarcated gray matter and white matter on the Strategically Acquired Gradient Echo (STAGE) images, and calculated values for susceptibility and R2* in these regions. Correlation analysis was performed between the R2* values and the susceptibility values. RESULTS: Besides the usual territories affected in ACP, we also discovered that the mammillary bodies and the lateral habenulae had significant increases in iron, and the hippocampus was severely affected both in terms of iron content and abnormal tissue signal. We also noted that the iron in the cortical gray matter appeared to be deposited in the inner layers. Moreover, several pathways between the superior colliculus and the pulvinar thalamus, between the caudate and putamen anteriorly and between the caudate and pulvinar thalamus posteriorly were also evident. Finally, R2* correlated strongly with the QSM data (R2 = 0.67, t = 6.78, p < 0.001). CONCLUSION: QSM and R2* have proven to be sensitive and quantitative means by which to measure iron content in the brain. Our findings included several newly noted affected brain regions of iron overload and provided some new aspects of iron metabolism in ACP that may be further applicable to other pathologic conditions. Furthermore, our study may pave the way for assessing efficacy of iron chelation therapy in these patients and for other common iron related neurodegenerative disorders.

Vascular, flow and perfusion abnormalities in Parkinson's disease.

BACKGROUND: Reduced flow into the brain or decreased jugular venous outflow from the brain may serve as a potential biomarker for Parkinson's disease (PD). Our goal was to compare the presence of vascular abnormalities, flow, and increases in midbrain iron content (a hallmark of the disease) in patients with PD. METHODS: A total of 85 PD patients and 85 healthy controls (HCs) were imaged at 3T. We assessed vascular abnormalities using magnetic resonance (MR) venography, average cerebral blood flow using 2D flow quantification, and substantia nigra iron content using susceptibility mapping. RESULTS: Fifty-two percent (52%) of the PD subjects showed venous structural and functional abnormalities in the two most severe categories, while ony 14% of the HC group showed these abnormalities. Total arterial flow (tA) was significantly lower for the PD group (10.9 ± 1.8 ml/s) compared to the HCs (11.6 ± 2.1 ml/s) (t = 2.28, p = 0.02). Of the PD patients (HCs), 42% (14%) had little flow on the left side. PD patients had higher heart rates and lower perfusion and the lower perfusion correlated with increased iron content in the substantia nigra. CONCLUSION: Some PD patients showed abnormal left internal jugular veins, lower tA, higher heart rates, and lower perfusion relative to HCs. These indicators could serve as early biomarkers for PD and create new avenues for future studies regarding the etiology of PD.

Iron Content in Deep Gray Matter as a Function of Age Using Quantitative Susceptibility Mapping: A Multicenter Study.

PURPOSE: To evaluate the effect of resolution on iron content using quantitative susceptibility mapping (QSM); to verify the consistency of QSM across field strengths and manufacturers in evaluating the iron content of deep gray matter (DGM) of the human brain using subjects from multiple sites; and to establish a susceptibility baseline as a function of age for each DGM structure using both a global and regional iron analysis. METHODS: Data from 623 healthy adults, ranging from 20 to 90 years old, were collected across 3 sites using gradient echo imaging on one 1.5 Tesla and two 3.0 Tesla MR scanners. Eight subcortical gray matter nuclei were semi-automatically segmented using a full-width half maximum threshold-based analysis of the QSM data. Mean susceptibility, volume and total iron content with age correlations were evaluated for each measured structure for both the whole-region and RII (high iron content regions) analysis. For the purpose of studying the effect of resolution on QSM, a digitized model of the brain was applied. RESULTS: The mean susceptibilities of the caudate nucleus (CN), globus pallidus (GP) and putamen (PUT) were not significantly affected by changing the slice thickness from 0.5 to 3 mm. But for small structures, the susceptibility was reduced by 10% for 2 mm thick slices. For global analysis, the mean susceptibility correlated positively with age for the CN, PUT, red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). There was a negative correlation with age in the thalamus (THA). The volumes of most nuclei were negatively correlated with age. Apart from the GP, THA, and pulvinar thalamus (PT), all the other structures showed an increasing total iron content despite the reductions in volume with age. For the RII regional high iron content analysis, mean susceptibility in most of the structures was moderately to strongly correlated with age. Similar to the global analysis, apart from the GP, THA, and PT, all structures showed an increasing total iron content. CONCLUSION: A reasonable estimate for age-related iron behavior can be obtained from a large cross site, cross manufacturer set of data when high enough resolutions are used. These estimates can be used for correcting for age related iron changes when studying diseases like Parkinson's disease, Alzheimer's disease, and other iron related neurodegenerative diseases.

Visualizing the lateral habenula using susceptibility weighted imaging and quantitative susceptibility mapping.

The habenulae consist of a pair of small nuclei which bridge the limbic forebrain and midbrain monoaminergic centers. They are implicated in major depressive disorders due to abnormal phasic response when provoked by a conditioned stimulus. The lateral habenula (Lhb) is believed to be involved in dopamine metabolism and is now a target for deep brain stimulation, a treatment which has shown promising anti-depression effects. We imaged the habenulae with susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) in order to localize the lateral habenula. Fifty-six healthy controls were recruited for this study. For the quantitative assessment, we traced the structure to compute volume from magnitude images and mean susceptibility bilaterally for the habenula on QSM. Thresholding methods were used to delineate the Lhb habenula on QSM. SWI, true SWI (tSWI), and QSM data were subjectively reviewed for increased Lhb contrast. SWI, QSM, and tSWI showed bilateral signal changes in the posterior location of the habenulae relative to the anterior location, which may indicate increased putative iron content within the Lhb. This signal behavior was shown in 41/44 (93%) subjects. In summary, it is possible to localize the lateral component of the habenula using SWI and QSM at 3 T.

STrategically Acquired Gradient Echo (STAGE) imaging, part III: Technical advances and clinical applications of a rapid multi-contrast multi-parametric brain imaging method.

One major thrust in radiology today is image standardization with a focus on rapidly acquired quantitative multi-contrast information. This is critical for multi-center trials, for the collection of big data and for the use of artificial intelligence in evaluating the data. Strategically acquired gradient echo (STAGE) imaging is one such method that can provide 8 qualitative and 7 quantitative pieces of information in 5 min or less at 3 T. STAGE provides qualitative images in the form of proton density weighted images, T1 weighted images, T2* weighted images and simulated double inversion recovery (DIR) images. STAGE also provides quantitative data in the form of proton spin density, T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid. STAGE uses vendors' product gradient echo sequences. It can be applied from 0.35 T to 7 T across all manufacturers producing similar results in contrast and quantification of the data. In this paper, we discuss the strengths and weaknesses of STAGE, demonstrate its contrast-to-noise (CNR) behavior relative to a large clinical data set and introduce a few new image contrasts derived from STAGE, including DIR images and a new concept referred to as true susceptibility weighted imaging (tSWI) linked to fluid attenuated inversion recovery (FLAIR) or tSWI-FLAIR for the evaluation of multiple sclerosis lesions. The robustness of STAGE T1 mapping was tested using the NIST/NIH phantom, while the reproducibility was tested by scanning a given individual ten times in one session and the same subject scanned once a week over a 12-week period. Assessment of the CNR for the enhanced T1W image (T1WE) showed a significantly better contrast between gray matter and white matter than conventional T1W images in both patients with Parkinson's disease and healthy controls. We also present some clinical cases using STAGE imaging in patients with stroke, metastasis, multiple sclerosis and a fetus with ventriculomegaly. Overall, STAGE is a comprehensive protocol that provides the clinician with numerous qualitative and quantitative images.

Imaging the Nigrosome 1 in the substantia nigra using susceptibility weighted imaging and quantitative susceptibility mapping: An application to Parkinson's disease.

Parkinson's disease (PD) is a clinically heterogeneous chronic progressive neuro-degenerative disease with loss of dopaminergic neurons in the nigrosome 1 (N1) territory of the substantia nigra pars compacta (SNpc). To date, there has been a major effort to identify changes in the N1 territory by monitoring increases of iron in the SNpc. However, there is no standard protocol being used to visualize or characterize the N1 territory. Therefore, the purpose of this study was to create a robust high quality, rapid imaging protocol, determine a slice by slice characterization of the appearance of N1 (the "N1 sign") and evaluate the loss of the N1 sign in order to differentiate healthy controls (HCs) from patients with PD. Firstly, one group of 10 HCs was used to determine the choice of imaging parameters. Secondly, another group of 80 HCs was used to characterize the appearance of the N1 sign and train the raters. In this step, the magnitude, susceptibility weighted images (SWI), quantitative susceptibility maps (QSM) and true SWI (tSWI) images were all reviewed using data from a 3D gradient recalled echo sequence. A resolution of 0.67 mm × 0.67 mm × 1.34 mm was chosen based on the ability to cover all the basal ganglia, midbrain and dentate nucleus with good signal-to-noise with echo times of 11 ms and 20 ms. Thirdly, 80 Parkinsonism and related disorders patients [idiopathic Parkinson's disease (IPD): 57; atypical parkinsonian syndromes (APs): 14; essential tremor (ET): 9] and one additional group of 80 age-matched HCs were blindly analyzed for the presence or absence of the N1 sign for a differential diagnosis. From the first group of 80 HCs, all of the 76 (100%) cases (4 were excluded due to motion artifacts) showed the N1 sign in one form or another after reviewing the first 5 caudal slices of the SN. For the second group of 80 HCs, 78 (97.5%) showed the N1 sign in at least 2 slices. Of the 80 Parkinsonism and related disorders patients, 32 (56.1%, 32/57) IPD and 6 (42.9%, 6/14) APs showed a bilateral loss of the N1 sign, 12 (21.1%, 12/57) IPD and 6 (42.9%, 6/14) APs showed the N1 sign unilaterally and 13 (22.8%, 13/57) IPD and 2 (14.2%, 2/14) APs showed the N1 sign bilaterally. Also, all 9 (100%, 9/9) ET patients showed the N1 sign bilaterally. The mean total structure and mean high susceptibility region for the SN for both IPD and APs patients with bilateral loss of N1 were higher than those of the HCs (p < 0.002). In conclusion, the N1 sign can be consistently visualized using tSWI with a resolution of at least 0.67 mm × 0.67 mm × 1.34 mm and can be seen in 95% of HCs.

Cerebral microbleed detection using Susceptibility Weighted Imaging and deep learning.

Detecting cerebral microbleeds (CMBs) is important in diagnosing a variety of diseases including dementia, stroke and traumatic brain injury. However, manual detection of CMBs can be time-consuming and prone to errors, whereas the current automatic algorithms for CMB detection are usually limited by large number of false positives. In this study, we present a two-stage CMB detection framework which contains a candidate detection stage based on a 3D fast radial symmetry transform of the composite images from Susceptibility Weighted Imaging (SWI), and a false positive reduction stage based on deep residual neural networks using both the SWI and the high-pass filtered phase images. While the SWI images provide exquisite sensitivity to the presence of blood products, the high-pass filtered phase images enable the differentiation of diamagnetic calcifications from paramagnetic microbleeds. The deep learning model was trained using 154 data sets, and the best models were selected using 25 validation data sets. Finally, the models were tested using 41 cases, including 13 hemodialysis cases, 9 traumatic brain injury cases, 9 stroke cases and 10 healthy controls. Using 3D SWI and high-pass filtered phase images as input, the best model led to a sensitivity of 95.8%, a precision of 70.9%, and 1.6 false positives per case. This model achieved similar performance to the most experienced human rater and outperformed recently reported CMB detection methods. This study demonstrates the potential of applying deep learning techniques to medical imaging for improving efficiency and accuracy in diagnosis.

Iron quantification in Parkinson's disease using an age-based threshold on susceptibility maps: The advantage of local versus entire structure iron content measurements.

BACKGROUND: Elevated brain iron has been observed in Idiopathic Parkinson's disease (IPD) within the deep gray matter. Using quantitative susceptibility mapping (QSM) and a thresholded high-iron region, we quantified iron content in the midbrain of patients with Parkinson's disease as a function of age. METHODS: We used MRI to scan 24 IPD patients at 3-Tesla. Susceptibility-weighted images were collected with the following parameters, TE: 6 and 20 ms, TR: 30 ms, FA: 15°, and resolution: 0.5 × 0.5 × 2.0 mm3. QSM images were reconstructed from the source phase images. Whole-region and thresholded high-iron (RII) region boundaries for the Substantia Nigra (SN) and Red Nucleus (RN) were traced. Iron content was measured via mean susceptibilities and volumes, which were compared between the groups, as well as between right and left side of the structures within groups. RESULTS: Twenty patients with mild to moderate IPD were used in this study. For the SN, mean RII and whole-region iron and volumes were higher in the IPD group compared to HC, as well as mean RII for the RN, while no differences were seen between the groups when considering whole-region mean susceptibility bilaterally for the RN. CONCLUSION: Using a two-region of interest analysis on QSM, we showed that abnormal iron occurs in IPD patients in the SN and with greater volumes compared to HC. This method may have application as a biomarker for disease diagnosis and early intervention.

Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

BACKGROUND: Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. METHODS: Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. RESULTS: A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = - 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = - 6.94) compared to the non-TC group (change = - 1.21, p for interaction = 0.07) and healthy controls (change = 0.09, p for interaction = 0.02). CONCLUSIONS: There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group; however, exploratory analyses demonstrated a reduction in both temporal lobe volume and oral reading recognition scores among patients on the TC regimen. These results suggest that different chemotherapy regimens may have differential effects on brain volume and cognition. Future, larger studies focusing on older adults with cancer on different treatment regimens are needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01992432 . Registered on 25 November 2013. Retrospectively registered.

STrategically Acquired Gradient Echo (STAGE) imaging, part II: Correcting for RF inhomogeneities in estimating T1 and proton density.

PURPOSE: To develop a method for mapping the B1 transmit (B1t) and B1 receive (B1r) fields from two gradient echo datasets each with a different flip angle and from these two images obtain accurate T1 and proton density (PD) maps of the brain. METHODS: A strategically acquired gradient echo (STAGE) data set is collected using two flip angles each with multiple echoes. The B1t field extraction was based on forcing cortical gray matter and white matter to have specific T1 values and fitting the resulting B1t field to a quadratic function. The B1r field extraction was based on synthesizing isointense images despite there being two or three tissue types present in the brain. This method was tested on 10 healthy volunteers and 20 stroke patients from data acquired at 3.0Tesla. RESULTS: With the knowledge of the B1t and B1r fields, the uniformity of tissue T1 and PD maps was considerably improved. T1 values were measured for both the midbrain and basal ganglia and found to be in good agreement with the literature. DISCUSSION AND CONCLUSIONS: STAGE provides a practical way to assess the B1t and the B1r fields which can then be used to correct for spatial variations in the images.

COnstrained Data Extrapolation (CODE): A new approach for high definition vascular imaging from low resolution data.

PURPOSE: To introduce a new approach to reconstruct high definition vascular images using COnstrained Data Extrapolation (CODE) and evaluate its capability in estimating vessel area and stenosis. MATERIALS AND METHODS: CODE is based on the constraint that the full width half maximum of a vessel can be accurately estimated and, since it represents the best estimate for the width of the object, higher k-space data can be generated from this information. To demonstrate the potential of extracting high definition vessel edges using low resolution data, both simulated and human data were analyzed to better visualize the vessels and to quantify both area and stenosis measurements. The results from CODE using one-fourth of the fully sampled k-space data were compared with a compressed sensing (CS) reconstruction approach using the same total amount of data but spread out between the center of k-space and the outer portions of the original k-space to accelerate data acquisition by a factor of four. RESULTS: For a sufficiently high signal-to-noise ratio (SNR) such as 16 (8), we found that objects as small as 3 voxels in the 25% under-sampled data (6 voxels when zero-filled) could be used for CODE and CS and provide an estimate of area with an error <5% (10%). For estimating up to a 70% stenosis with an SNR of 4, CODE was found to be more robust to noise than CS having a smaller variance albeit a larger bias. Reconstruction times were >200 (30) times faster for CODE compared to CS in the simulated (human) data. CONCLUSION: CODE was capable of producing sharp sub-voxel edges and accurately estimating stenosis to within 5% for clinically relevant studies of vessels with a width of at least 3pixels in the low resolution images.

Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.

Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18-74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.

Database integration of protocol-specific neurological imaging datasets.

For many years now, Magnetic Resonance Innovations (MR Innovations), a magnetic resonance imaging (MRI) software development, technology, and research company, has been aggregating a multitude of MRI data from different scanning sites through its collaborations and research contracts. The majority of the data has adhered to neuroimaging protocols developed by our group which has helped ensure its quality and consistency. The protocols involved include the study of: traumatic brain injury, extracranial venous imaging for multiple sclerosis and Parkinson's disease, and stroke. The database has proven invaluable in helping to establish disease biomarkers, validate findings across multiple data sets, develop and refine signal processing algorithms, and establish both public and private research collaborations. Myriad Masters and PhD dissertations have been possible thanks to the availability of this database. As an example of a project that cuts across diseases, we have used the data and specialized software to develop new guidelines for detecting cerebral microbleeds. Ultimately, the database has been vital in our ability to provide tools and information for researchers and radiologists in diagnosing their patients, and we encourage collaborations and welcome sharing of similar data in this database.