System, method, and computer accessible medium for accelerated imaging sequences for intracranial hemorrhage screening

Abstract

Exemplary systems, methods, and computer-accessible medium are provided that can generating functional magnetic resonance imaging data (MRI) for an entire brain in a fraction of the time of traditional MRI. Thus, exemplary systems, methods, and computer-accessible medium can be provided that can obtain a single average of an echoplanar image (EPI) sequence to generate functional MRI data, and acquire or generate a fully-formed image of the entire brain based on the functional MRI data using the single average of EPI sequence. This fully formed brain image can be obtained in, e.g., approximately 1-2 seconds (of course other timing of acquisition is possible). Further, the single average of the EPI sequence can acquire a fully formed brain image by acquiring all of k-space with Cartesian sampling.

Description

SYSTEM, METHOD, AND COMPUTER ACCESSIBLE MEDIUM FOR ACCELERATED IMAGING SEQUENCES FOR INTRACRANIAL HEMORRHAGE SCREENINGCROSS REFERENCE TO RELATED APPLICATION(S)

[0001] This application relates to and claims the benefit of priority from U.S. Provisional Patent Application No. 63 / 640,657, filed on April 30, 2024, the entire disclosure of which is incorporated herein by reference.FIELD OF THE DISCLOSURE

[0002] The present disclosure relates generally to systems, methods and computer-accessible medium for detecting intracranial hemorrhage in patients evaluated for anti-amyloid therapy, and more specifically to systems, methods, and computer accessible medium for rater assessment of highly-accelerated imaging (e.g., Magnetic Resonance Imaging - “MRI”) sequences for detecting intracranial hemorrhage in patients evaluated for anti-amyloid therapy.BACKGROUND INFORMATION

[0003] Cerebral microbleed(s) (CMB) are small hemosiderin deposits in the brain parenchyma attributed to the rupture of small vessels. The prevalence of CMB by MRI varies with age - e.g. 18% of patients aged 60-69 have CMB whereas 38% of patients over 80 have CMB (see, e.g., Ref. 1, 2). In vivo, CMB can be best detected on 2D T2*-weighted gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI) MRI sequences (see, e.g., Ref. 3). CMB can be associated with amyloid angiopathy, cognitive impairment, transient ischemic attack or stroke, and higher overall mortality (see, e.g., Ref. 4-6). A less common type of hemorrhage, superficial siderosis (SS) represents hemosiderin deposits along the pial surfaces of the brain, attributed to chronic sequalae of incompletely cleared subarachnoid hemorrhage (see, e.g., Ref. 7).

[0004] An identification of CMB and SS is clinically important, particularly in the therapeutic management of FDA-approved anti-amyloid-beta (anti-AP) immunotherapies. Patients undergoing these treatments are at increased risk of CMB and SS, especially during the first 3-4 months of therapy, referred to as amyloid-related imaging abnormalities-hemorrhage subtype (ARIA-H) (see, e.g., Ref. 8, 9). A -positive patients with more than 4 CMB, or an area of SS on pre-treatment screening MRI are excluded from receiving anti-AP immunotherapy. If treatmentis initiated, patients undergo multiple scheduled MRIs (5-6 for most clinical therapy protocols) to screen for new ARIA-H. In prior studies, during 18 months of treatment with Lecanemab or Donanemab, 14% and 27% of patients developed CMB, whereas 6% and 16% of patients developed SS, respectively (see, e.g., Ref. 10, 11). Thus, the accurate detection of hemorrhage with specific MRI sequences is a critical requirement for screening and monitoring anti-Ap therapy (see, e.g., Ref. 10-12).

[0005] Current MRI sequences can vary in sensitivity and efficiency for detecting intracranial hemorrhage. The SWI sequence is superior to 2D T2* -weighted GRE sequences for the detection of CMB (see, e.g., Ref. 13, 14). However, SWI generally has worse tissue contrast and takes much longer to acquire with increased vulnerability to image degradation from patient motion (see, e.g., Ref. 15). The 2D T2*-weighted GRE sequence can be faster to acquire with less motion sensitivity and can be more widely available across different institutions and countries. This may be why GRE was used instead of SWI in recent pivotal trials of current anti-Ap immunotherapies. Acquisition speed for individual sequences can also be important to limit the total MRI table time so that patients can finish the study and do not move during any portion of the scan. Patients unable to complete repeat diagnostic MRIs (e.g., due to motion) are not considered for anti-Ap therapy.

[0006] Thus, there is a need for highly accelerated echo-planar (EPI) substitutions to the standard GRE and SWI sequences that are non-inferior to standard sequences for the detection of cerebral microbleeds (CMBs) and superficial siderosis (SS) (comprising ARIA-H) in patients being evaluated for dementia and anti-amyloid therapy, which can address and / or overcome at least some of the deficiencies described herein above.SUMMARY OF EXEMPLARY EMBODIMENTS

[0007] The following is intended to be a brief summary of the exemplary embodiments of the present disclosure, and is not intended to limit the scope of the exemplary embodiments.

[0008] In some exemplary embodiments of the present disclosure, exemplary systems, methods, and computer accessible medium can be provided which can generate functional magnetic resonance imaging data in a fraction of the time of traditional MRI. For example, exemplary systems, methods, and computer-accessible medium can be configured or utilized to apply a single average of an exemplary echoplanar image (EPI) sequence to acquire a fully formed image of theentire brain. This fully formed brain image can be obtained, e.g., in 1-2 seconds. Further, the single average of the exemplary EPT sequence can be used to acquire a fully formed brain image by acquiring all of k-space with Cartesian sampling. The exemplary EPI sequence of exemplary systems, methods, and computer-accessible medium can be, e.g., T2*-weighted so as to be sensitive to a Blood Oxygenation Level Dependent (BOLD) contrast, and a temporal resolution for detecting the BOLD contrast can be a temporal resolution (“TR”) of the sequence.

[0009] These and other objects, features and advantages of the exemplary embodiments of the present disclosure will become apparent upon reading the following detailed description of the exemplary embodiments of the present disclosure, when taken in conjunction with the appended claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Further objects, features and advantages of the present disclosure will become apparent from the following detailed description taken in conjunction with the accompanying Figures showing illustrative embodiments of the present disclosure, in which:

[0011] Figure 1 is an exemplary flow diagram of patient inclusion and exclusion for highly accelerated echo-planar (EPI) substitutions according to exemplary embodiments of the present disclosure;

[0012] Figures 2A-2D are exemplary graphs illustrating receiver operating characteristic curves for each individual rater and series, where Figure 2A is a CMB detection for GRE and aGRE, Figure 2B is SS detection for GRE and aGRE, Figure 2C is a CMB detection for SWI and aSWI, and Figure 2D is a SS detection for SWI and aSWI, according to exemplary embodiments of the present disclosure;

[0013] Figures 3A-3D are exemplary images comparing a right parietal subcortical cerebral microbleed in a 76-year-old male with Alzheimer’s disease on gradient-recalled echo (Figure 3 A), accelerated gradient-recalled echo-echo-planar (Figure 3B), susceptibility-weighted imaging (Figure 3C) and accelerated susceptibility -weighted imaging-echo-planar substitution (Figure 3D) sequences, according to exemplary embodiments of the present disclosure;

[0014] Figures 4A-4D are exemplary images comparing an area of right frontal superficial siderosis (arrow) in an 86-y ear-old female with Alzheimer’s disease on gradient-recalled echo (Figure 4A), accelerated gradient-recalled echo-echo-planar (Figure 4B), susceptibility-weightedimaging (Figure 4C) and accelerated susceptibility-weighted imaging-echo-planar substitution (Figure 4D) sequences with similar conspicuity, according to exemplary embodiments of the present disclosure;

[0015] Figure 5A is an exemplary violin plot illustrating scores of raters for image quality on gradient-recalled echo sequences according to exemplary embodiments of the present disclosure;

[0016] Figure 5B is an exemplary violin plot illustrating scores of raters for image quality on susceptibility-weighted imaging sequences according to exemplary embodiments of the present disclosure;

[0017] Figure 5C is an exemplary violin plot illustrating score of raters for motion on gradient- recalled echo sequences according to exemplary embodiments of the present disclosure;

[0018] Figure 5D is an exemplary violin plot illustrating raters’ scores for motion on susceptibility-weighted imaging sequences according to exemplary embodiments of the present disclosure;

[0019] Figures 6A-6D are exemplary images illustrating motion reduction by the accelerated sequences in an 81 -year-old male patient with Alzheimer’ s disease, where Figure 6A is a gradient- recalled echo sequence, Figure 6B is an accelerated gradient-recalled echo-echo-planar sequence, Figure 6C is a susceptibility-weighted imaging sequence, and Figure 6D is an accelerated susceptibility-weighted imaging-echo-planar substitution, according to exemplary embodiments of the present disclosure; and

[0020] Figure 7 is a block diagram of an exemplary embodiment of a system according to the present disclosure.

[0021] Throughout the drawings, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the present disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments and is not limited by the particular embodiments illustrated in the figures and the appended claims.DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0022] The following description of exemplary embodiments provides non-limiting representative examples referencing numerals to particularly describe features and teachings of different exemplary aspects and exemplary embodiments of the present disclosure. The exemplaryembodiments described should be recognized as capable of implementation separately, or in combination, with other exemplary embodiments from the description of the exemplary embodiments. A person of ordinary skill in the art reviewing the description of the exemplary embodiments should be able to learn and understand the different described aspects of the present disclosure. The description of the exemplary embodiments should facilitate understanding of the exemplary embodiments of the present disclosure to such an extent that other implementations, not specifically covered but within the knowledge of a person of skill in the art having read the description of embodiments, would be understood to be consistent with an application of the exemplary embodiments of the present disclosure.

[0023] Echo-planar-accelerated gradient-recalled echo and susceptibility-weighted MRI sequences or the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can reduce scan time e.g., 78-81% in cognitive impairment patients screened for anti-amyloid-beta immunotherapy without degrading diagnostic performance at detecting cerebral microbleeds or superficial siderosis.

[0024] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can generate, create and / or facilitate an accelerated EPI sequence to reproduce the in-plane resolution and slice thickness of the standard gradient-recalled echo (GRE) sequence used for ARIA monitoring during the pivotal phase III drug trial and FDA approval of lecanemab, reducing scan time e.g., 85% from 90 to 14 sec. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can further accelerate a 1.5-mm isotropic SWI sequence with a similar approach, reducing scan time e.g., 78% from 192 to 42 sec.

[0025] To validate exemplary systems, methods, and computer accessible medium according to exemplary embodiments of the present disclosure, raters evaluated both accelerated and standard GRE and SWI sequences from 25 consecutive positive (presence of CMB or SS) and 25 consecutive negative patients undergoing FDG-PET MRI for the evaluation of dementia between April-July 2023. The raters quantified both the number of CMBs (1-10 or “>I0”) and areas of superficial siderosis (0, 1, 2 or >2). Additionally, raters scored image quality (1-5, with 5 being “excellent”) and degree of motion (1-3, with 3 being “no motion”) on an ordinal scale. In exemplary systems, methods, and computer accessible medium according to exemplary embodiments of the present disclosure, statistical agreement for sequences regarding CMB / SSdetection, image quality and motion can be assessed with Wilcoxon signed-rank and McNemar tests. Simple kappa co-efficients can be used to determine inter- and intrarater agreement.

[0026] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can utilize one or more exemplary echoplanar image (EPI) sequence architecture to generate functional MRI data. For example, the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can use a single average of the exemplary EPI sequence(s) to acquire all of k-space with Cartesian sampling such that a fully formed image of the entire brain can be obtained in 1-2 sec. This EPI sequence can be T2*-weighted such that it is sensitive to Blood Oxygenation Level Dependent (BOLD) contrast as oxy- and deoxy-hemoglobin have slightly different signal intensities due to changes in their magnetic properties. For task-based fMRI, a patient or subject can perform a task like moving their right fingers, and because of neurovascular uncoupling, the amount of oxygenated blood flow to the contralateral left hand knob of the precentral gyms increases (and this increases the MRI signal). In exemplary systems, methods, and computer accessible medium according to exemplary embodiments of the present disclosure, the exemplary fMRI sequence can be acquired continuously - the temporal resolution (“TR”) for detecting the BOLD effect is the TR of the sequence. This can comprise, e.g., 80 or more single “averages” or “volumes” that can be acquired (~2 min 40 sec or longer) and the signal change can be measured over time.

[0027] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can leverage the speed that EPI can be used to generate or create an image or volume, but also that EPI is sensitive not just to BOLD effect, but hemorrhage. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can adjust a standard EPI fMRI sequence to reproduce the same geometry as the hemorrhage-sensitive sequence used for the key phase III drug trial for Lecanemab, an anti-amyloid immunotherapy (and the same sequence described in FDA approval of the drug) - 1 ,5-mm in-plane with 5-mm thick slices. This alternate sequence according to the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can have the following additional parameters (TR / TE = 3250 / 31 ms, flip angle = 90 degrees, 1 average, Partial Fourier 7 / 8, iPAT factor = 2). The exemplary systems, methods, and computer accessible medium according to the exemplaryembodiments of the present disclosure can establish improved image quality through parallel imaging, but this can require initial calibration scans that add time to the protocol.

[0028] This exemplary approach, according to exemplary systems, methods, and computer accessible medium according to exemplary embodiments of the present disclosure, can take, e.g., about 13 sec instead of 90 sec with the standard sequence. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can perform an EPI mimic of the standard gradient echo with or without parallel imaging, with or without multiband (also called simultaneous multi-slice) and potentially of different geometries. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can also generate, create and / or facilitate a version that can reproduce, e.g., a l-5mm isotropic resolution SWI sequence with the following parameters (TR / TE = 8370 / 35 ms, flip angle = 90 degrees, 1 average, Partial Fourier 7 / 8, iPAT factor = 2). In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, this version takes 33 sec instead of ~ 3 min.Exemplary MethodsExemplary Validation and Patient Characteristics

[0029] In evaluating the performance of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, a retrospective review can be performed. For example, Figure 1 can illustrate the exemplary criteria for inclusion or exclusion. At step 110, a dataset may be bounded (e.g., of 326 consecutive patients who underwent integrated PET-MRI for cognitive impairment at a single tertiary academic medical center in a large metropolitan area). Inclusion criteria for the performance evaluation can include prior evaluation by a physician with expertise in cognitive impairment and imaging study with both accelerated and standard GRE and SWI sequences. At step 120 the subset of patients reported as positive for hemorrhage can be collected. Similarly, at step 130, the subset of patients reported as negative for hemorrhage can be collected. At step 140, some number of patients from the positive hemorrhage group can be excluded based on a number of factors, such as incomplete imaging, vascular lesion, corrupted data, and excessive motion. At step 150, some number of patients from the negative hemorrhage group can be excluded based on a number of factors, such as incomplete imaging and hemorrhage not detected in clinical report. At steps 160 and 170, a subset of theremaining patients from each group may be selected for performance evaluation of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure.Exemplary Imaging Protocol

[0030] In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, after standard preparation and confirmation of blood glucose e.g., < 200 mg / dL, patients can be injected with 4 mCi (148MBq) of Fluorodeoxy glucose (FDG), then rested quietly in a dimly lit room for e.g., 40 minutes with eyes open. Patients can then be positioned on a PET / MRI scanner such as a 3T Biograph mMR PET / MRI scanner (e.g., Siemens Healthineers, Forchheim, Germany). The PET imaging portion of a protocol according to the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can include e.g., 20 minutes of list-mode data acquired with atlas-based product attenuation correction (see, e.g., Ref. 17). MRI sequences (e.g., 4) sensitive for hemorrhage can be included; these sequences can include standard GRE and SWI and two EPI-accelerated substitutions (see below).

[0031] The standard GRE sequence parameters can be, e g., TR / TE = 800 / 19.9 ms, flip angle 20°, slice thickness 5 mm, FOV 192 x 220 mm and pixel bandwidth 200 Hz with a 90-second acquisition time (this can closely match a sequence used for phase-3 trials of anti-A0 immunotherapies) (see, e.g., Ref. 10, 11). Standard SWI parameters were can be, e.g., TR / TE = 26 / 20 ms, flip angle 15°, slice thickness 1.5 mm, FOV 201 x 230 mm, pixel bandwidth 170 Hz with a 192-second acquisition time. The accelerated protocols of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can be achieved by the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure using an EPI sequence with 2- factor GRAPPA acceleration. In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, two preparatory EPI shots can be used to drive the magnetization to steady state, then a separate EPI shot can be used to acquire reference lines for GRAPPA acceleration. The last shot can be performed with the TE and echo train length (ETL) optimized for motion-robust imaging, and the entire volume can be acquired within the prescribed TR in an interleaved fashion. The EPI-accelerated GREsubstitution (aGRE) sequence parameters can be, e.g., TR / TE = 3250 / 23 ms, flip angle 90°, ETL 142, section thickness 5 mm, FOV 220 x 220 mm and bandwidth 1530 Hz with a 17-second acquisition time. The EPI-accelerated SWI substitution (aSWI) sequence parameters can be, e.g., TR / TE = 9240 / 26 ms, flip angle 90°, ETL 149, slice thickness 1.5 mm, FOV 244 x 244 mm and pixel bandwidth 1165 Hz with a 42-second acquisition time. All 4 sequences can have e.g., 1.5 x 1.5 mm2in-plane resolution.Exemplary Rater Assessment of Images

[0032] Rater assessment in the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can focus on comparing diagnostic accuracy, image quality and motion sensitivity for GRE versus aGRE, and SWI versus aSWI. Comparison of GRE to SWI in the detection of CMB has been previously reported (see, e. ., Ref 13, 14). Imaging studies can be rated in independent, blinded fashion by 3 board-certified neuroradiologists. The data can be organized by an independent disinterested party. Some number of patient studies can be included (e.g., 50); in this example, the first 25 consecutive eligible cases reported as positive, and the first 25 consecutive cases reported as negative for hemorrhage in the original radiology reports can be included. In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, the last five consecutive cases from each group can be duplicated to assess intra-rater agreement (e.g., 10 total). In this specific example, this resulted in “60 cases”, each with 4 different sequences (e.g., 240 total assessments). While the incidence of hemorrhage in the source population was 15%, the sample can be enriched to an equal portion of positive and negative cases to improve the statistical power of the study when comparing the sequences. The raters were not informed of the prevalence of hemorrhage in the dataset. Review of cases can take place over multiple sessions and times (e.g., over four sessions two weeks apart). Each session can contain e.g., 60 randomly ordered cases of GRE, aGRE, aSWI or SWI contrast (each case can be the entire axial series in scrollable form).

[0033] In this specific example, Raters reported the number of CMB up to 10, or greater than 10, and reported SS as 0, 1, 2 or >3 areas consistent with ARIA-H monitoring guidelines (see, e.g., Ref. 16). Raters were asked their subjective impression of imaging quality using a five-point ordinal scale [e.g., excellent (5), good (4), acceptable (3), poor quality (2) or unacceptable (1)] and image motion degradation using a three-point ordinal scale [e.g., no motion (3), mild motion (2),or substantial motion degradation (1)]. Gold standard assessment of the number of CMB and SS were determined separately for the GRE and SWI sequences by consensus between the neuroradiology fellow and an attending with 10+ years’ experience (where gold standard assessment is independent of the raters).Exemplary Statistical Analysis

[0034] In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, statistical analysis can be performed using SPSS (e.g., IBM Corp., Armonk, NY) with the R extension for certain tests (i.e. DeLong’s test and Fleiss Weighted Kappa). A P-value of < 0.05 can be considered significant, without correction for false discovery (i.e. Bonferroni) as this may only increase the probability of failing to detect a difference between the sequences. For each rater (and in aggregate based on majority read), sensitivity, specificity, positive and negative predictive value, and area under the curve (AUC) can be calculated for CMB and SS detection in a binary fashion (e.g., “0” = absent, “1” = present) for each sequence compared to gold standard. The predictive values can be corrected post hoc for actual population hemorrhage prevalence (e.g., 15%). DeLong’s test can be used to compare AUCs.

[0035] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can assess quantification of CMB and SS for each rater (and in aggregate based on mean of the raters) between accelerated and standard GRE and SWI using the Wilcoxon signed-rank test. Mean absolute error, bias and effect size can be calculated. Correlation can be assessed using Kendall’s tau.

[0036] With the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, inter-rater and intra-rater agreement between sequences for CMB or SS binary detection and quantification can be assessed using a weighted Fleiss kappa and Cohen’s weighted kappa respectively.

[0037] Median and interquartile ranges can be computed for image quality and motion. Overall subjective preference and perceived motion ordinal scores can be compared with Wilcoxon signed- rank tests. In a post hoc analysis, image quality scores can be converted to a binary classification of unacceptable (e.g., scores 1-2) and acceptable (e.g., scores 3-5), then can be compared using aMcNemar’s test. Inter- and intra-rater agreement can be assessed using a weighted Fleiss kappa and Cohen’s weighted kappa respectively.Exemplary ResultsExemplary Subject Characteristics

[0038] The clinical reports documented CMB in 49 of 326 (15.3%) and SS in 8 / 326 (2.5%) of consecutive patients undergoing combined FDG-PET MRI for cognitive impairment between April 24thto July 28th, 2023. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure excluded 8 total cases (5 with hemorrhage and 3 without hemorrhage) for incomplete imaging, underlying vascular malformation, excessive motion and incomplete data, as reflected in Figure 1. Otherwise, the first 25 consecutive cases reported as positive and first 25 consecutive cases reported as negative for CMB were extracted for rater assessment (6 positive cases also had SS) - the two groups appeared similar, as reflected in Table 1.Table 1. Comparison of Patients with and without Hemorrhage Consecutively Enrolled for The Rater Study. * Number subjects with this type of hemorrhage, median number of CMB or SS for positive cases and the interquartile range based on unblinded consensus review (“gold standard”). IQR = Interquartile range, MMSE = Mini Mental Status Exam, MoCA = Montreal Cognitive Assessment, CMB = cerebral microbleed(s), SS = superficial siderosis, MCI = mild cognitive impairment, AD = Alzheimer’s disease, DLB = Dementia with Lewy Bodies, VCI = Vascular cognitive impairment, FTLD = frontotemporal lobar degenerationExemplary CMB and SS Detection

[0039] Figures 3A-3D and 4A-4D illustrate selected examples comparing detection of CMB and SS respectively across all 4 sequences. For example, Figures 3A-3D show four MRI images comparing a right parietal subcortical cerebral microbleed (CMB) in a 76-year-old male with Alzheimer’s disease. Figure 3 A shows a GRE sequence, Figure 3B shows an aGRE sequence, Figure 3C shows a SWI sequence, and Figure 3D shows an aSWI sequence. This CMB finding was identified on the aGRE, rather than the GRE, by 2 of 3 raters. All raters detected this CMB on aSWI and SWI. Similarly, Figure 4 shows four MRI images comparing an area of right frontal superficial siderosis (arrow) in an 86-y ear-old female with Alzheimer’s disease. Figure 4A shows a GRE sequence, Figure 4B shows an aGRE sequence, Figure 4C shows a SWI sequence, and Figure 4D shows an aSWI sequence with similar conspicuity, detected by all raters on all sequences.

[0040] The aggregate sensitivity, specificity, negative and positive predictive value, and AUC for detecting CMB or SS with GRE and SWI, as well as these values for aGRE and aSWI as provided by the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure are detailed in Table 2.Table 2. Diagnostic Performance of 4 MRI Sequences Compared to Gold Standard for Presence of Cerebral Microbleed(s) (CMB) And Superficial Siderosis (SS) [Binary Classification, Aggregate of 3 Raters], I' Raw fractions not applicable as value corrected for prevalence. *The AUC for standard and echo-planar-accelerated sequences were compared with DeLong’s test with the 95% confidence interval for the true difference provided in brackets. PPV = positive predictive value, NPV = negative predictive value, GRE = gradient-recalled echo, aGRE = accelerated gradient-recalled echo-echo-planar, SWI = susceptibility-weighted imaging, aSWI = accelerated susceptibility-weighted imaging-echo-planar substitution

[0041] Individual rater values are provided in Tables 3 and 4.Table 3. Diagnostic Performance of 4 MRI Sequences Compared to Gold Standard for Presence of Cerebral Microbleed(s) (CMB) for Each Rater [Binary Classification], fRaw fractions not applicable as calculations corrected for prevalence. *The AUC for standard and EPI-accelerated sequences were compared with DeLong’s test with the 95% confidence interval for the true difference provided in brackets. PPV = positive predictive value, NPV = negative predictive value, GRE = gradient-recalled echo, aGRE = accelerated gradient-recalled echo-echo-planar, SWI = susceptibility-weighted imaging, aSWI = accelerated susceptibility-weighted imaging-echo-planar substitutionTable 4. Diagnostic Performance of 4 MRI Sequences Compared to Gold Standard for Presence of Superficial Siderosis (SS) for Each Rater [Binary Classification], fRaw fractions not applicable as calculations corrected for prevalence. *The AUC for standard and EPI-accel erated sequences were compared with DeLong’s test with the 95% confidence interval for the true difference provided in parentheses. PPV = positive predictive value, NPV = negative predictive value, GRE = gradient-recalled echo, aGRE = accelerated gradient-recalled echo-echo-planar, SWI = susceptibility-weighted imaging, aSWI = accelerated susceptibility-weighted imaging-echo-planar substitution

[0042] For both the detection of CMB and SS, the diagnostic performance of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, e.g., GRE versus aGRE or SWI versus aSWI appear similar and consistently excellent (e.g., AUC > 0.800) without statistical differences. In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, the 95% confidence interval for the maximum potential true absolute difference for CMB detection between GRE-aGRE and SWI-aSWI AUCs can be e.g., 0.11 and 0.23 respectively. Figure 2 illustrates the receiver operating characteristic curves for detecting CMB and SS using GRE, aGRE, SWI and aSWI for for each individual rater and series. Figures 2A and 2C reflectCMB detection for GRE and aGRE, and SWI and aSWI, respectively, and Figures 2B and 2D show graphs of an exemplary SS detection for GRE and aGRE, and SWI and aSWI, respectively. Rater 1 GRE and rater 2 aGRE curves overlap for CMB detection (see Figure 2A) and rater 1 SWI and rater 2 aSWI overlap for SS detection (see Figure 2D).Exemplary CMB Quantification

[0043] In mean aggregate, the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can show that CMB quantification was not different between GRE and aGRE, and the two sequences can show moderate correlation (e.g., r = 0.606, Table 5).Table 5. Diagnostic Performance of 4 MRI Sequences Compared to Gold Standard for Presence of Cerebral Microbleed(s) (CMB) [Quantitative Comparison, Mean of 3 Raters]

[0044] In contrast, the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can result in there being fewer CMB counted by raters for aSWI compared to SWI (e.g., P = 0.014, Table 5) and the correlation can be moderate, but weaker (e.g., r = 0.391, Table 5). Rater specific differences for quantification are provided in Table S3. There were an insufficient number of SS cases with more than 1 area of SS for meaningful comparison.Table 6. Diagnostic Performance of 4 MRI Sequences Compared to Gold Standard for Presence of Cerebral Microbleed(s) (CMB) for Each Rater [Quantitative Comparison]Exemplary Inter- and Intra-rater Agreement

[0045] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can provide substantial inter-rater agreement for CMB detection for GRE, aGRE and SWI, as reflected in table 7, but moderate for aSWI (e.g., 0.463).Table 7. Inter-Rater Agreement for Detection of Cerebral Microbleed(s) (CMB) Or Superficial Siderosis (SS), and Quantification of CMB Using 4 Different MRI Sequences (3 Raters)

[0046] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can provide moderate inter-rater agreement for SS detection for GRE and aGRE, and can provide higher for both SWI and aSWI, as reflected in Table 7. The kappa coefficients for CMB and SS detection can be consistently lower for aGRE and aSWI (e.g., 17.8 - 28.7% reductions). Kappa coefficients for inter-rater agreement for quantification can be lower than detection - in some exemplary embodiments, there may be no difference between GRE and aGRE, while agreement for quantification can be fair (e.g., 0.244) with aSWI. In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, mean weighted kappa for intra-rater agreement for CMB detection can be substantial for aSWI and near perfect for GRE, aGRE and SWI, as reflected in Table 8.Table 8. Intra-Rater Agreement for the Detection and Quantification of Cerebral Microbleed(s) (CMB)

[0047] Following a similar trend, the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can provide intra-rater agreement for quantification of CMB that is substantial to moderate but can be lower with the accelerated sequences.Exemplary Image quality and motion analysis

[0048] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can provide a median image quality score for 3 raters for both GRE and aGRE that can be good or acceptable, as reflected in Figures 5A-5D and Table 9.Table 9. Perceived Image Quality and Motion For 4 MR1 Sequences by Rater

[0049] Figures 5 A and 5B show violin plots of rater’s scores for image quality, whereas Figures 5C and 5D show violin plots of rater’s scores for motion. The light circle represents the median, while the width and number of dots reflect the number of responses for each ordinal score.

[0050] In the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure, for aGRE, 2 of 3 radiologists reported 1 point or less reduction in median perceived image quality on an ordinal scale (Table 9, P < 0.05). When image quality was redefined post hoc as unacceptable (e.g., score 1-2) vs acceptable (e.g., 3-5),only 1 of 3 raters perceived a statistically significant reduction of acceptable studies (e.g., 80% to 52%, P = 0.007). The aSWI of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can be perceived as lower quality by all 3 raters (P <0.05, Figure 5D, Table 9). When image quality was redefined post hoc as unacceptable (e.g., score 1-2) vs acceptable (e.g., 3-5), 2 of 3 raters still perceived a statistically significant reduction of acceptable studies (P <0.05). All 3 raters scored motion similarity with GRE and aGRE but perceived less motion on aSWI compared to SWI (P < 0.05, Figures 6A-6D). Figures 6A-6D provide a series of MRI images showing motion reduction by the accelerated sequences in an 81-year-old male patient with Alzheimer’s disease. Two foci of cerebral microbleed (CMB) in the left cerebellar hemisphere (arrow) are obscured on the heavily motion- degraded gradient-recalled echo sequence in Figure 6A, but become visible due to reduced motion on the accelerated gradient-recalled echo-echo-planar sequence in Figure 6B. The CMB are also well depicted on the accelerated susceptibility-weighted imaging-echo-planar substitution sequence in Figure 6D, which shows less motion than the susceptibility-weighted imaging sequence in Figure 6C.

[0051] Figure 7 shows a block diagram of an exemplary embodiment of a system according to the present disclosure. For example, exemplary procedures in accordance with the present disclosure described herein can be performed by a processing arrangement and / or a computing arrangement (e.g., computer hardware arrangement) 705. Such processing / computing arrangement 705 can be, for example entirely or a part of, or include, but not limited to, a computer / processor 710 that can include, for example one or more microprocessors, and use instructions stored on a computer- accessible medium (e.g., RAM, ROM, hard drive, or other storage device).

[0052] As shown in Figure 7, for example, a computer-accessible medium 715 (e.g., as described herein above, a storage device such as a hard disk, floppy disk, memory stick, CD-ROM, RAM, ROM, etc., or a collection thereof) can be provided (e.g., in communication with the processing arrangement 705). The computer-accessible medium 715 can contain executable instructions 720 thereon. In addition or alternatively, a storage arrangement 725 can be provided separately from the computer-accessible medium 715, which can provide the instructions to the processing arrangement 705 so as to configure the processing arrangement to execute certain exemplary procedures, processes, and methods, as described herein above, for example.

[0053] Further, the exemplary processing arrangement 705 can be provided with or include an input / output ports 735, which can include, for example a wired network, a wireless network, the internet, an intranet, a data collection probe, a sensor, etc. As shown in Figure 7, the exemplary processing arrangement 705 can be in communication with an exemplary display arrangement 730, which, according to certain exemplary embodiments of the present disclosure, can be a touchscreen configured for inputting information to the processing arrangement in addition to outputting information from the processing arrangement, for example. Further, the exemplary display arrangement 730 and / or a storage arrangement 725 can be used to display and / or store data in a user-accessible format and / or user-readable formatExemplary Discussion

[0054] The EPI-accel erated GRE and SWI substitutions of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure used with patients undergoing ARIA-H screening can reduce scan time by, e.g., 1.2 minutes (81%) and 2.5 minutes (78%) respectively. In a 3-rater blinded assessment, aGRE and aSWI may not be significantly different for detecting CMB and SS compared to standard GRE and SWI respectively (p = 0.152-0.660). The AUCs for all 4 sequences can appear similar to those reported in a recent study of GRE for detecting ARIA-H with or without assistance from artificial intelligence software (see, e.g., Ref. 18). The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure may not provide differences in CMB quantification between GRE and aGRE, and may only provide a moderate correlation between the two sequences (r = 0.606). This can be of particular importance since guidelines suggest use of GRE for detecting ARIA-H in patients considering or on anti-Ap immunotherapy (see, e.g., Ref. 16).

[0055] The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can provide attractive time savings and similar diagnostic performance of aGRE and aSWI. Raters can generally perceive decreased image quality for both aGRE and aSWI. It is intuitive that faster scans can be associated with reduced perceived image quality as also reported by other studies (see, e.g., Ref. 19, 20), and the difference can be more pronounced with aSWI. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can improve imagequality by further altering the sequence (e.g. more averages or multi-shot EPI) or deep learning image denoising (see, e.g., Ref. 21). Compared to the GRE-aGRE pair, the correlation between SWI and aSWI for CMB quantification can be weaker (e.g., 0.391) and fewer CMB may be detected with aSWI than SWI. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can show that interrater agreement is moderate across all 4 sequences for CMB or SS detection but can be lower for aGRE and aSWI. Agreement for CMB quantification can be lower for all 4 sequences, but can be lowest for aSWI. The exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can provide artificial intelligence software that may be capable of improving agreement for detection and quantification of hemorrhage for aGRE and aSWI.

[0056] The benefits and limitations of the aGRE or aSWI of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can help radiologists decide whether to use these sequences, and when. The time savings from aGRE or aSWI can reduce scan time and help protocols to conform better to scheduled MRI slots. The shorter scan times of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can also reduce motion degraded scans as raters observed for aSWI versus SWI. If the modified EPI sequences provided by the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure contain multiple volumes (i.e. more than 1 signal average) those volumes can be re-aligned with rigid registration to further reduce macroscopic head motion during the acquisition like how motion is monitored and removed from functional MRI EPI data. In a patient who is moving or can only tolerate limited scan times, aGRE or aSWI of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure may be the only alternative to “no data.”

[0057] Existing literature provides other methods to accelerate MRI for hemorrhage detection. Earlier studies found single-shot EPI inferior to GRE (see, e.g., Ref. 22, 23). This may reflect increased geometric distortion and decreased imaging quality for EPI compared to GRE (and SWI). The updated single-shot EPI-accelerated sequences provided by the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure include more recent parallel imaging and multiband modifications to improveperformance (see, e.g., Ref. 24). Multi-shot EPI may further reduce artifacts and improve image quality, albeit with increased scan time (see, e.g., Ref. 25). Previous works described 2D interleaved EPI or 3D short-axis propeller EPI to accelerate SWI, but did not assess diagnostic performance (see, e.g., Ref. 26 and 27). Under sampled data with compressed sensing (CS) image reconstruction also can reduce SWI scan time (see, e.g., Ref. 28), although the ultimate recommended CS acceleration described previously was slower than the aSWI of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure. Rater assessment of CS-SWI in that study focused specifically on visualization of the substantia nigra, internal cerebral vein and basilar artery (not hemorrhage), and data was acquired with a less commonly used 32-channel head coil precluding direct comparisons to the current results. Deep learning reconstructions of under sampled or EPI-accel erated GRE or SWI may also be helpful in future investigations (see, e.g., Ref. 29).

[0058] EPI-accelerated GRE and SWI substitutions of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can maintain diagnostic performance for CMB and SS detection for a common clinical indication with e.g., -80% reductions in scan time. These faster acquisitions improve the chances of obtaining diagnostic data, reduce motion degradation and increase scanner throughput, while potentially mildly degrading image quality and rater consistency. The aGRE and aSWI sequences of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure can have immediate practical benefits as a sequence substitution in patient populations requiring rapid imaging (e.g., acutely ill, pediatric, claustrophobic or cognitively impaired patients) or in imaging studies with a low pretest probability for hemorrhage. Using aGRE or aSWI of the exemplary systems, methods, and computer accessible medium according to the exemplary embodiments of the present disclosure for ARIA-H screening can be feasible but may be best introduced gradually or with Al support (see, e.g., Ref. 18) as radiologists become more familiar with this altered image contrast.

[0059] Throughout the disclosure, the following terms take at least the meanings explicitly associated herein, unless the context clearly dictates otherwise. The term “or” is intended to mean an inclusive “or.” Further, the terms “a,” “an,” and “the” are intended to mean one or more unless specified otherwise or clear from the context to be directed to a singular form.

[0060] In this description, numerous specific details have been set forth. It is to be understood, however, that implementations of the disclosed technology can be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description. References to “some examples,” “other examples,” “one example,” “an example,” “various examples,” “one embodiment,” “an embodiment,” “some embodiments,” “example embodiment,” “various embodiments,” “one implementation,” “an implementation,” “example implementation,” “various implementations,” “some implementations,” etc., indicate that the implementation(s) of the disclosed technology so described may include a particular feature, structure, or characteristic, but not every implementation necessarily includes the particular feature, structure, or characteristic. Further, repeated use of the phrases “in one example,” “in one exemplary embodiment,” or “in one implementation” does not necessarily refer to the same example, exemplary embodiment, or implementation, although it may.

[0061] As used herein, unless otherwise specified the use of the ordinal adjectives “first,” “second,” “third,” etc., to describe a common object, merely indicate that different instances of like objects are being referred to, and are not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking, or in any other manner.

[0062] While certain implementations of the disclosed technology have been described in connection with what is presently considered to be the most practical and various implementations, it is to be understood that the disclosed technology is not to be limited to the disclosed implementations, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0063] This written description uses examples to disclose certain implementations of the disclosed technology, including the best mode, and also to enable any person skilled in the art to practice certain implementations of the disclosed technology, including making and using any devices or systems and performing any incorporated methods. The patentable scope of certain implementations of the disclosed technology is defined in the paragraphs, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the paragraphs if they have structural elements that do not differ from the literal languageof the paragraphs, or if they include equivalent structural elements with insubstantial differences from the literal language of the paragraphs.EXEMPLARY REFERENCES

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Claims

WHAT IS CLAIMED TS;1. A method for generating functional magnetic resonance imaging data (MRI) for an entire brain, comprising: obtaining a single average of an echoplanar image (EPI) sequence to generate functional MRI data; and acquiring or generating a fully-formed image of the entire brain based on the functional MRI data using the single average of EPI sequence.

2. The method of claim 1, wherein the fully formed image of the entire brain is obtained in less than 2 seconds.

3. The method of claim 1, wherein the fully-formed image of the entire brain is obtained in approximately 1 second.

4. The method of claim 1, wherein the single average of the EPI sequence acquires all of k-space information using a Cartesian sampling procedure.

5. The method of claim 1, wherein the EPI sequence is T2*-weighted so as to be sensitive to a Blood Oxygenation Level Dependent (BOLD) contrast.

6. The method of claim 5, wherein a temporal resolution for detecting the BOLD contrast is a temporal resolution (“TR”) of the EPI sequence.

7. A system for generating functional magnetic resonance imaging data, comprising: at least one computer processor which is configured to:• obtain a single average of an echoplanar image (EPI) sequence to generate functional MRI data; and• acquire or generate a fully-formed image of the entire brain based on the functional MRI data using the single average of EPI sequence.

8. The system of claim 7, wherein the fully formed image of the entire brain is obtained in less than 2 seconds.

9. The system of claim 7, wherein the fully-formed image of the entire brain is obtained in approximately 1 second.

10. The system of claim 7, wherein the single average of the EPI sequence acquires all of k- space information using a Cartesian sampling procedure.

11. The system of claim 7, wherein the EPI sequence is T2*-weighted to be sensitive to a Blood Oxygenation Level Dependent (BOLD) contrast.

12. The system of claim 11, wherein a temporal resolution for detecting the BOLD contrast is a temporal resolution (“TR”) of the EPI sequence.

13. A non-transitory computer accessible medium which includes software thereon for generating functional magnetic resonance imaging data, wherein, when at least one computer processor execute the software, the computer processor is configured to perform the procedures, comprising: obtaining a single average of an echoplanar image (EPI) sequence to generate functional MRI data; and acquiring or generating a fully-formed image of the entire brain based on the functional MRI data using the single average of EPI sequence.

14. The computer accessible medium of claim 13, wherein the fully formed image of the entire brain is obtained in less than 2 seconds.

15. The computer accessible medium of claim 13, wherein the fully formed image of the entire brain is obtained in approximately 1 second.

16. The computer accessible medium of claim 13, wherein the single average of the EPI sequence acquires all of k-space using a Cartesian sampling procedure.

17. The computer accessible medium of claim 13, wherein the EPI sequence is T2* -weighted to be sensitive to a Blood Oxygenation Level Dependent (BOLD) contrast.

18. The computer accessible medium of claim 17, wherein a temporal resolution for detecting the BOLD contrast is a temporal resolution (“TR”) of the EPI sequence.

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