Strategically Acquired Gradient Echo (STAGE) Imaging, part IV: Constrained Reconstruction of White Noise (CROWN) Processing as a Means to Improve Signal-to-Noise in STAGE Imaging at 3 Tesla.

Increasing the signal-to-noise ratio (SNR) has always been of critical importance for magnetic resonance imaging. Although increasing field strength provides a linear increase in SNR, it is more and more costly as field strength increases. Therefore, there is a major effort today to use signal processing methods to improve SNR since it is more efficient and economical. There are a variety of methods to improve SNR such as averaging the data at the expense of imaging time, or collecting the data with a lower resolution, all of these methods, including imaging processing methods, usually come at the expense of loss of image detail or image blurring. Therefore, we developed a new mathematical approach called CROWN (Constrained Reconstruction of White Noise) to enhance SNR without loss of structural detail and without affecting scanning time. In this study, we introduced and tested the concept behind CROWN specifically for STAGE (strategically acquired gradient echo) imaging. The concept itself is presented first, followed by simulations to demonstrate its theoretical effectiveness. Then the SNR improvement on proton spin density (PSD) and R2⁎ maps was investigated using brain STAGE data acquired from 10 healthy controls (HCs) and 10 patients with Parkinson's disease (PD). For the PSD and R2* maps, the SNR and CNR between white matter and gray matter were improved by a factor of 1.87 ± 0.50 and 1.72 ± 0.88, respectively. The white matter hyperintensity lesions in PD patients were more clearly defined after CROWN processing. Using these improved maps, simulated images for any repeat time, echo time or flip angle can be created with improved SNR. The potential applications of this technology are to trade off the increased SNR for higher resolution images and/or faster imaging.

Brain iron deposition and movement disorders in hereditary haemochromatosis without liver failure: A cross-sectional study.

BACKGROUND AND PURPOSE: Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. METHODS: This is a cross-sectional study. Consecutive subjects with HFE-haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age- and sex-matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping-based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. RESULTS: Fifty-two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty-five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. CONCLUSIONS: Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH.

Three-dimensional simultaneous brain mapping of T1, T2, T2∗ and magnetic susceptibility with MR Multitasking.

PURPOSE: To develop a new technique that enables simultaneous quantification of whole-brain T1 , T2 , T2∗ , as well as susceptibility and synthesis of six contrast-weighted images in a single 9.1-minute scan. METHODS: The technique uses hybrid T2 -prepared inversion-recovery pulse modules and multi-echo gradient-echo readouts to collect k-space data with various T1, T2, and T2∗ weightings. The underlying image is represented as a six-dimensional low-rank tensor consisting of three spatial dimensions and three temporal dimensions corresponding to T1 recovery, T2 decay, and multi-echo behaviors, respectively. Multiparametric maps were fitted from reconstructed image series. The proposed method was validated on phantoms and healthy volunteers, by comparing quantitative measurements against corresponding reference methods. The feasibility of generating six contrast-weighted images was also examined. RESULTS: High quality, co-registered T1 , T2 , and T2∗ susceptibility maps were generated that closely resembled the reference maps. Phantom measurements showed substantial consistency (R2 > 0.98) with the reference measurements. Despite the significant differences of T1 (p < .001), T2 (p = .002), and T2∗ (p = 0.008) between our method and the references for in vivo studies, excellent agreement was achieved with all intraclass correlation coefficients greater than 0.75. No significant difference was found for susceptibility (p = .900). The framework is also capable of synthesizing six contrast-weighted images. CONCLUSION: The MR Multitasking-based 3D brain mapping of T1 , T2 , T2∗ , and susceptibility agrees well with the reference and is a promising technique for multicontrast and quantitative imaging.

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.

Multi-Echo Quantitative Susceptibility Mapping for Strategically Acquired Gradient Echo (STAGE) Imaging.

PURPOSE: To develop a method to reconstruct quantitative susceptibility mapping (QSM) from multi-echo, multi-flip angle data collected using strategically acquired gradient echo (STAGE) imaging. METHODS: The proposed QSM reconstruction algorithm, referred to as "structurally constrained Susceptibility Weighted Imaging and Mapping" scSWIM, performs an ℓ 1 and ℓ 2 regularization-based reconstruction in a single step. The unique contrast of the T1 weighted enhanced (T1WE) image derived from STAGE imaging was used to extract reliable geometry constraints to protect the basal ganglia from over-smoothing. The multi-echo multi-flip angle data were used for improving the contrast-to-noise ratio in QSM through a weighted averaging scheme. The measured susceptibility values from scSWIM for both simulated and in vivo data were compared to the: original susceptibility model (for simulated data only), the multi orientation COSMOS (for in vivo data only), truncated k-space division (TKD), iterative susceptibility weighted imaging and mapping (iSWIM), and morphology enabled dipole inversion (MEDI) algorithms. Goodness of fit was quantified by measuring the root mean squared error (RMSE) and structural similarity index (SSIM). Additionally, scSWIM was assessed in ten healthy subjects. RESULTS: The unique contrast and tissue boundaries from T1WE and iSWIM enable the accurate definition of edges of high susceptibility regions. For the simulated brain model without the addition of microbleeds and calcium, the RMSE was best at 5.21ppb for scSWIM and 8.74ppb for MEDI thanks to the reduced streaking artifacts. However, by adding the microbleeds and calcium, MEDI's performance dropped to 47.53ppb while scSWIM performance remained the same. The SSIM was highest for scSWIM (0.90) and then MEDI (0.80). The deviation from the expected susceptibility in deep gray matter structures for simulated data relative to the model (and for the in vivo data relative to COSMOS) as measured by the slope was lowest for scSWIM + 1%(-1%); MEDI + 2%(-11%) and then iSWIM -5%(-10%). Finally, scSWIM measurements in the basal ganglia of healthy subjects were in agreement with literature. CONCLUSION: This study shows that using a data fidelity term and structural constraints results in reduced noise and streaking artifacts while preserving structural details. Furthermore, the use of STAGE imaging with multi-echo and multi-flip data helps to improve the signal-to-noise ratio in QSM data and yields less artifacts.

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.

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.

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.

Retinal image registration using geometrical features.

In this study, we have introduced an accurate retinal images registration method using affine moment invariants (AMI's) which are the shape descriptors. First, some closed-boundary regions are extracted in both reference and sensed images. Then, AMI's are computed for each of those regions. The centers of gravity of three pairs of regions which have the minimum of distances are selected as the control points. The region matching is performed by the distance measurements of AMI's. The evaluation of region matching is performed by comparing the angles of three triangles which are built on these three-point pairs in reference and sensed images. The parameters of affine transform can be computed using these three pairs of control points. The proposed algorithm is applied on the valid DRIVE database. In general (for the case, each sensed image is produced by rotating, scaling, and translating the reference image with different angles, scale factors, and translation factors), the success rate and accuracy is 95 and 96 %, respectively.