Simultaneous imaging of radiation-induced cerebral microbleeds, arteries and veins, using a multiple gradient echo sequence at 7 Tesla
2014; Wiley; Volume: 42; Issue: 2 Linguagem: Inglês
10.1002/jmri.24802
ISSN1522-2586
AutoresWei Bian, Suchandrima Banerjee, Douglas Kelly, Christopher P. Hess, Peder E. Z. Larson, Susan M. Chang, Sarah J. Nelson, Janine M. Lupo,
Tópico(s)MRI in cancer diagnosis
ResumoJournal of Magnetic Resonance ImagingVolume 42, Issue 2 p. 269-279 Original ResearchFree Access Simultaneous imaging of radiation-induced cerebral microbleeds, arteries and veins, using a multiple gradient echo sequence at 7 Tesla Wei Bian MS, Wei Bian MS The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, California, USA Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorSuchandrima Banerjee PhD, Suchandrima Banerjee PhD Global Applied Science Laboratory, GE Healthcare, Menlo Park, California, USASearch for more papers by this authorDouglas A.C. Kelly PhD, Douglas A.C. Kelly PhD Global Applied Science Laboratory, GE Healthcare, San Francisco, California, USASearch for more papers by this authorChristopher P. Hess MD, PhD, Christopher P. Hess MD, PhD Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorPeder E.Z. Larson PhD, Peder E.Z. Larson PhD orcid.org/0000-0003-4183-3634 The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, California, USA Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorSusan M. Chang MD, Susan M. Chang MD Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorSarah J. Nelson PhD, Sarah J. Nelson PhD The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, California, USA Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorJanine M. Lupo PhD, Corresponding Author Janine M. Lupo PhD Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USAAddress reprint requests to: J.M.L., Byers Hall UCSF, Box 2532, 1700 4th Street, Suite 303, San Francisco, CA 94158. E-mail: janine.lupo@ucsf.eduSearch for more papers by this author Wei Bian MS, Wei Bian MS The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, California, USA Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorSuchandrima Banerjee PhD, Suchandrima Banerjee PhD Global Applied Science Laboratory, GE Healthcare, Menlo Park, California, USASearch for more papers by this authorDouglas A.C. Kelly PhD, Douglas A.C. Kelly PhD Global Applied Science Laboratory, GE Healthcare, San Francisco, California, USASearch for more papers by this authorChristopher P. Hess MD, PhD, Christopher P. Hess MD, PhD Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorPeder E.Z. Larson PhD, Peder E.Z. Larson PhD orcid.org/0000-0003-4183-3634 The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, California, USA Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorSusan M. Chang MD, Susan M. Chang MD Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorSarah J. Nelson PhD, Sarah J. Nelson PhD The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, California, USA Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USASearch for more papers by this authorJanine M. Lupo PhD, Corresponding Author Janine M. Lupo PhD Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USAAddress reprint requests to: J.M.L., Byers Hall UCSF, Box 2532, 1700 4th Street, Suite 303, San Francisco, CA 94158. E-mail: janine.lupo@ucsf.eduSearch for more papers by this author First published: 04 December 2014 https://doi.org/10.1002/jmri.24802Citations: 15AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Background The purpose of this study was to implement and evaluate the utility of a multi-echo sequence at 7 Tesla (T) for simultaneous time-of-flight (TOF) MR-angiography (MRA) and susceptibility-weighted imaging (SWI) of radiation-induced cerebral microbleeds (CMBs), intracranial arteries, and veins. Methods A four-echo gradient-echo sequence was implemented on a 7T scanner. The first echo was used to create TOF-MRA images, while the remaining echoes were combined to visualize CMBs and veins on SWI images. The sequence was evaluated on eight brain tumor patients with known radiation-induced CMBs. Single-echo images were also acquired to visually and quantitatively compare the contrast-to-noise ratio (CNR) of small- and intermediate-vessels between acquisitions. The number of CMBs detected with each acquisition was also quantified. Statistical significance was determined using a Wilcoxon signed-rank test. Results Compared with the single-echo sequences, the CNR of small and intermediate arteries increased 7.6% (P < 0.03) and 9.5% (P = 0.06), respectively, while the CNR of small and intermediate veins were not statistically different between sequences (P = 0.95 and P = 0.46, respectively). However, these differences were not discernible by visual inspection. Also the multi-echo sequence detected 18.3% more CMBs (P < 0.008) due to higher slice resolution. Conclusion The proposed 7T multi-echo sequence depicts arteries, veins, and CMBs on a single image to facilitate quantitative evaluation of radiation-induced vascular injury. J. Magn. Reson. Imaging 2015;42:269–279. Radiation Therapy (RT) is a widely used treatment in the management of patients with malignant brain tumors.1 It is often used either in conjunction with chemotherapy after surgical resection to reduce residual tumor burden or alone in surgically inaccessible tumors.1 Despite its effectiveness and recent modern advances to constrain dose distribution more effectively to the tumor, collateral injury to normal brain tissue is always present and includes coagulative necrosis, white matter demyelization, cortical atrophy, and endothelial proliferation.2 RT is also correlated with the development of vascular abnormalities including cavernous malformations,3 moyamoya-like progressive steno-occlusive disease,4 accelerated atherosclerosis, and other forms of large vessel arteriopathy.5 At the microvascular level, histopathological analyses reveal a spectrum of radiation injury that includes endothelial disruption, fibrinoid necrosis, luminal narrowing, and occlusion, which leads to the formation of cerebral microbleeds (CMBs) in otherwise normal-appearing brain tissue.6, 7 These hemosiderin-containing deposits begin to appear approximately two years post-RT and continue to increase in number over time.8-11 More recent studies have demonstrated a correlation between the number of CMBs and the dose and the target volume defined for radiation therapy,10, 11 pointing to the potential use of these lesions as a surrogate quantitative marker of radiation injury. While the origin of CMBs has not been completely defined, ionizing radiation is known to have a greater effect on smaller caliber vasculature and is more likely to damage arteries than veins.6 A strategy to noninvasively image arteries and veins simultaneously, and to assess the spatial distribution of CMBs relative to these structures would help to establish a relationship between CMB formation and underlying vascular pathology, and aid in clinical and basic science studies of CMB that arise in cerebral amyloid angiopathy (CAA),12 stroke,13 Alzheimer's disease,14 traumatic brain injury (TBI),15 mild cognitive impairment,16 and dementia.17 CMBs can be observed noninvasively on MR images using T2*-weighted gradient echo sequences as small hypointense lesions, often with spherical shape.18 These imaging features are enhanced by susceptibility-weighted imaging (SWI), an MR imaging technique that is more sensitive to CMBs than conventional T2*-weighted imaging 8-10, 19 and permits accurate visualization of intracranial veins as hypointense due to the presence of iron-containing deoxyhemoglobin.20 In contradistinction, arterial contrast in three-dimensional (3D) time-of-flight (TOF) MR angiography (MRA) is determined by flow-related enhancement and background suppression.21 While the utility of these sequences for characterizing CMBs 8-10, 19 and intracranial vessels 20-24 has been demonstrated, accounting for prescanning, the combined time spent on the two separate sequences can be 15 to 20 min. Also, accurate registration is nearly impossible to attain due to the lack of both anatomical contrast and structural similarity between the TOF-MRA and SWI, in addition to the blurring of sub-millimeter CMBs and microvasculature after the interpolation step of the registration. Thus, a combined MRA-SWI sequence using multiple gradient echoes can not only reduce scan time but also obviate the need for image coregistration, which would benefit our understanding of CMB formation by providing metrics that reflect the interaction among vascular structures that are not confounded by inaccuracies in the coregistration. The ability to obtain a simultaneous acquisition of 3D TOF-MRA and SWI in a single imaging sequence with multiple echoes has been recently demonstrated in a normal volunteer at 3 Tesla (T).25 The elevated SNR, heightened background suppression for TOF-MRA, and amplified susceptibility contrast for SWI available at 7T demonstrates the potential of this platform to provide excellent delineation of both CMBs and microvasculature.8, 22 While previous studies have demonstrated the capability of implementing a dual- or multi-echo acquisition on normal volunteers,25-28 there have been no efforts at simultaneously optimizing contrast of CMBs and microvasculature, creating combined SWI images from multiple echoes, reconstruction and processing improvements, or clinical evaluation. The purpose of this study was to design a 7T multi-echo sequence and SWI reconstruction pipeline using data from multiple echoes, and assess resulting image quality by comparing it with that of separate TOF-MRA and SWI acquisitions. By using the sequence, we aim to obtain high-resolution vascular images for the simultaneous depiction of arteries, veins, and CMBs in patients with brain tumors treated with prior radiation therapy. Method and Materials Sequence Design A multi-echo sequence was created by adding three additional echoes to a single-echo, multi-slab 3D spoiled gradient recalled (SPGR) echo sequence with TOF capabilities on a GE 7T system (GE Healthcare, Waukesha, WI) equipped with a 32-channel phased array receive coil insert situated within a volume transmit coil (Nova Medical, Wilmington, MA). The first echo was used to create TOF-MRA images, while the remaining three echoes were combined to generate a composite SWI image. The sequence diagram of the final empirically optimized acquisition scheme is shown in Figure 1. Because adequate background suppression and heightened contrast of arteries on the TOF-MRA images requires minimizing the echo time (TE) of the first echo and overall repetition time (TR), flow compensation was performed only in the readout direction and all echoes were partially acquired with a 65% sampling coverage. This resulted in a TE1/TE2/TE3/TE4 of 2.7/10.5/13.2/20.9 ms and a TR of 40ms when using a bandwidth of 41.67 kHz, in-plane matrix of 512 × 384, and FOV of 24 cm. A small flip angle of 25° was used for excitation and a multiple overlapping thin-slab acquisition (MOTSA),24 an approach that is widely used for TOF-MRA, was applied to all four echoes. Three slabs with thirty-six 1-mm-thick slices and 12 slices of overlap were used to minimize signal saturation for the TOF-MRA images from the first echo while maintaining a large enough 3D volume to achieve adequate SNR for SWI image obtained from the later echoes. The acquisition was accelerated in the phase encoding direction with an autocalibrating partially parallel imaging strategy that used an acceleration factor of 3 and 16 auto-calibrating lines, resulting in a total acquisition time of 10.6 min. Figure 1Open in figure viewerPowerPoint The diagram of the proposed 3D multi-echo spoiled gradient echo sequence. The sequence contains 4 partially acquired (65%) echoes at the TEs (arrows) of 2.7, 10.4, 13.2, and 20.9 ms. The data from the first echo are used to generate TOF-MRA, while the data from the remaining 3 echoes are combined to generate SWI images. Flow compensation was performed only in the readout direction using a prewind bipolar gradient for the first echo and flyback gradients for the other 3 echoes. (RF: rf pulse; SS: Slice selection gradient; PE: Phase encoding gradient). Image Reconstruction The raw complex k-space data from all 32 coils were transferred off-line to a Linux workstation, where postprocessing was performed using in-house programs developed with MATLAB 7.0 software (MathWorks, Natick, MA). Our processing pipeline for reconstruction and combination of multi-echo, multi-channel data is illustrated in Figure 2. For each individual coil, missing phase-encoding lines were recovered using an autocalibrating parallel imaging reconstruction method: auto-calibrating reconstruction for Cartesian sampling (ARC).29 For reconstruction of magnitude images at each echo, all partially-acquired k-space echoes were recovered to their full extent by projection onto convex sets (POCS).30 The full FOV 512 × 384 k-space data from all echoes were then zero-padded out in the phase-encoding direction to create a 512 × 512 matrix before taking the inverse Fourier transform. Magnitude images from each coil were combined using the root sum of squares 31 and skull stripped using FMRIB Software Library's (FSL) Brain Extraction Tool (BET).32 The final magnitude images from the first echo were used for TOF-MRA while those from the final three echoes were used for subsequent SWI processing described as follows. Figure 2Open in figure viewerPowerPoint Image reconstruction and postprocessing pipelines for TOF-MRA and SWI images acquired from the multi-echo sequence. During SWI processing, the data from the final three echoes were, first, processed individually before a composite SWI image was created (Fig. 2). To generate high-pass filtered phase images for each coil, the complex k-space data after ARC reconstruction from echoes 2–4 were zero-filled in the frequency-encoding direction, followed by homodyne filtering with Hanning filter sizes of 72, 88, and 104 for the 2nd, 3rd, and 4th echoes, respectively. These filter sizes were empirically determined for each TE to preserve local contrast while removing macroscopic background phase wraps. The high-pass filtered phase images from each coil were combined by weighted sum (weighted by the square of corresponding magnitude intensity). The phase images from echoes 2∼4 was then averaged to produce a mean phase image, from which a negative phase mask was created by linearly scaling negative phase values between zero and one and setting positive phase values to one. This mean phase image was later examined to confirm the absence of calcification in these lesions, as paramagnetic microbleeds are hypointense on both SWI and phase images while diamagnetic calcifying lesions appear hyperintense on phase images even though they are hypointense on SWI images. The mean magnitude image from the three echoes was also produced and multiplied with the phase mask 4 times to generate the final composite SWI image. Clinical Evaluation The proposed sequence was evaluated on eight patients (four males and four females with a mean age of 45.2 years and a range from 29.8 to 67.1 years) who were specifically recruited for this study because of the presence of multiple confirmed CMBs due to prior external beam radiation therapy of a resected glioma. The time between the 7T imaging examination and start of radiation ranged from 3 to 15 years. The study was approved by our institutional Committee for Human Research, and written informed consent was obtained from all patients. Conventional single-echo TOF-MRA and SWI sequences with the same acceleration, FOV, image matrix, flip angle, and coverage were scanned in addition to the combined multi-echo sequence on all patients. The other parameters used for each sequence are listed in Table 1. Table 1. Acquisition Parameters for Single- and Multi-echo Sequencesaa Parameters that are the same to all 3 sequences: FOV 24 cm, flip angle 25o, acquisition matrix 512 × 384, in-plane resolution 0.46 × 0.63 mm2, and acceleration factor 3. 3D SWI 3D TOF-MRA 3D Multi-echo MRA/SWI Slice thickness 2 mm 1 mm 1 mm Slab thickness 1 slab 3 slabs 3 slabs 36 slice 30 slices/slab 36 slices /slab 6 overlapping slices 12 overlapping slices Bandwidth 15.25 kHz 41.76 kHz 41.76 kHz K-Space coverage Full Partial (65%) Partial (65%) TR 50 ms 30 ms 40 ms TE(s) 16 ms 2.7 ms 2.7, 10.5, 13.2, 20.9 ms Acquisition time 4 mins/50 s 6 mins/40 s 10 mins/36 s a Parameters that are the same to all 3 sequences: FOV 24 cm, flip angle 25o, acquisition matrix 512 × 384, in-plane resolution 0.46 × 0.63 mm2, and acceleration factor 3. Data Analysis To evaluate the quality of the depiction of arteries, veins, and CMBs in images generated from the combined multi-echo sequence, maximum and minimum intensity projections (maxIP and minIP) through 8-mm-thick slices were created for all TOF-MRA and SWI images, respectively. These projected images were used to both count the number of CMBs detected on SWI images and quantify the contrast-to-noise ratio (CNR) of small- (diameter ≤1 mm) and intermediate- (1 mm < diameter ≤2 mm) sized vessels. CMBs were defined as round, hypointense foci with diameters less than 5 mm on consecutive slices. An automated detection algorithm 33 that was highly sensitive to radiation-induced CMBs on minIP SWI images was used to identify CMBs in approximately 1 min. The algorithm used geometric features such as shape, area, and circularity to distinguish potential CMBs from other sources of hypointense signal, including linear vessels and susceptibility artifacts. The output from the automatic detection was then independently inspected by two raters (W.B. and J.M.L.) in random order to remove any remaining false positives, add any CMBs that were missed by the automated detection, and count the identified CMBs. The raters had 7 and 11 years experience, respectively, in brain tumor imaging and, more specifically, 4 and 6 years identifying and evaluating CMB under the guidance of a board certified neuroradiologist (C.P.H.), who also visually evaluated the overall image quality of arteries and veins on images from both single- and multi-echo sequences. The mean phase images were also examined by W.B. and J.M.L. to verify that all identified CMBs were not due to the presence of calcification, which would appear hyperintense on phase images because calcium is diamagnetic.8 The inter-rater agreement of the CMB counting was measured by calculating an intraclass correlation coefficient (ICC) based on absolute agreement. The final CMB counts that were obtained from each rater were averaged to quantify the number of true CMBs for each patient. CNR was calculated from 10 regions of interest (ROIs) for each size vessel on both the TOF-MRA and SWI images. Each vessel segment selected was carefully matched in size and length between the single- and multi-echo sequences to minimize any effects of motion or partial voluming between scans and spaced to span the entire supratentorial brain coverage to minimize any bias from spatial variations in contrast due to the parallel reconstruction. This resulted in 40 total vessel segments for each patient. ROIs of background brain parenchyma were generated by first dilating each vessel ROI (with a kernel size of .5 mm and 1 mm for small and intermediate vessels, respectively) and then subtracting the vessel ROI from the dilated ROI. Examples of vessel and background ROIs are illustrated in Figure 3. Noise was estimated from the standard deviation of a homogeneous region of corpus callosum for both the TOF-MRA and SWI according to Denk and Rauscher.34 CNR was calculated as the difference in the median values between the vessel and background ROIs divided by the noise. The 10 CNR values from each vessel type were then averaged for each patient. A Wilcoxon signed-rank test was used to test for significant differences in the averaged CNR and the number of CMBs between image acquisitions. Figure 3Open in figure viewerPowerPoint ROIs of veins and arteries were defined on TOF-MRA (A) and SWI (B) images, which were maximally and minimally projected over 8mm thickness, respectively. ROIs were paired between the multi-echo images (top rows in A & B) and corresponding single-echo images (bottom rows in A & B). Each vessel ROI (pink) was dilated (green) to create a corresponding background tissue ROI after subtracting out the original vessel ROI. The ROIs were defined for intermediate diameter (between 1 and 2 mm, large arrows) and small diameter (less than 1 mm, small arrows) arteries and veins. Results The benefit of combining data from echoes 2–4 in the creation of a composite SWI image compared with using data from a single echo time is illustrated in Figure 4A. SNR was improved for the combined composite SWI image compared with the SWI image generated from echo 3 (whose TE was similar to that of the single-echo SWI sequence), as evident by a more homogeneous appearance of the ventricles on the composite image due to the reduction of noise. Plots of average CNR for both small and intermediate veins on minIP SWI images from echo 3 and all echoes combined for all eight patients are shown in Figure 4B. Combining the 2nd−4th echoes of the multi-echo sequence resulted in an average CNR that was 52.2% and 45.0% higher than those measured on the minIP SWI images from the third echo only for small and intermediate veins, respectively (both statistically significant with P < 0.008). Figure 4Open in figure viewerPowerPoint A: Magnitude, phase, SWI, and minIP images from echo 3 (top row) and combined processing (bottom row), where both magnitude and phase images from echoes 2 to 4 were first created individually and then averaged to generate mean magnitude and phase images before generating the final SWI images. The SNR was greatly improved for the combined composite SWI image compared with that from the echo 3 (whose TE was similar to that of single-echo SWI sequence), which is evident by a more homogeneous display of the ventricles on the former. B: Plots of average CNR for both small and intermediate veins from minIP SWI images of echo 3 and the composite SWI image for all 8 patients. The composite SWI image had significantly higher CNR for both vein sizes in all patients. Visually, the overall image quality was comparable between the single- and multi-echo sequences, with a slight degradation of background suppression on the TOF-MRA and higher noise level on the SWI images generated from the multi-echo sequence. Both small and intermediate veins were similarly depicted on the single- and multi-echo sequences. In addition, single-echo SWI was able to better delineate large draining veins, while smaller veins and CMBs were observed on the multi-echo SWI images, primarily due to its higher slice resolution. A typical example of this is shown in Figure 5A. On the other hand, all arteries appeared similarly on the multi-echo and single-echo TOF-MRA despite the slightly worse background suppression of the multi-echo acquisition, due to the longer TR (Fig. 5B). Figure 5Open in figure viewerPowerPoint The minIP SWI (A) and maxIP TOF-MRA (B) for both multi-echo and individual single-echo sequences. For illustration purposes, a local region (dashed-box) from each is zoomed in and shown on the right column. On (A), single-echo SWI better delineates larger veins (large arrows) because of its high CNR, while multi-echo SWI better illustrates smaller veins and CMBs primarily due to its higher slice resolution. On (B), all arteries including both larger (large arrows) and smaller (small arrows) arteries have similar contrast on both multi- and single-echo TOF-MRA, despite the slightly worse background suppression of the multi-echo acquisition due to a longer TR. C: Plots of average CNR for each type of vessel from all 8 patients' images acquired from both multi- and single-echo sequences. Except for small arteries, which had a slightly significantly higher CNR on TOF-MRA from the multi-echo sequence, all other vessels had comparable CNRs between images from the multi- and single-echo sequences. Figure 5C shows plots of average CNR for each type of vessel calculated from the multi- and single-echo sequences from all eight patients. On average, CNRs of small and intermediate veins were not significantly different between the single- and multi-echo SWI images (3% difference with P = 0.95 for small veins and 6.7% difference with P = 0.46 for intermediate veins). The average CNR of small and intermediate arteries on TOF-MRA increased 7.6% and 9.5%, respectively, for the multi-echo sequence compared with values obtained from the single-echo sequence. Although this difference was statistically significant for small arteries (P < 0.03), it did not reach significance for intermediate ones (P = 0.06). Figure 6A displays an overlay of a thresholded slice of TOF-MRA (maxIP over 8 mm) on the minIP SWI image from the multi-echo sequence. From this overlay, it is apparent that some CMBs are clearly arising from venous vessels (as denoted by the pink dashed-box) while others appear to originate from arterioles (green dashed-box). Table 2 lists the number of CMBs detected from both sequences for each patient. None of the identified CMBs were found to be calcifications after visual inspection of the mean phase images. Both raters consistently detected more CMBs on the multi-echo minIP SWI images than on the single-echo minIP images (P < 0.008 for rater 1 and P < 0.024 for rater 2). The ICC between the two raters on CMB counting from all eight patients was 0.995 for both the single- and multi-echo images. Because the ICC calculation is heavily influenced by the number of CMBs and can be artificially elevated when the variability in CMB counts among patients is large, we repeated the calculation excluding the two patients who had more than 200 CMBs. This more reliable estimation of inter-rater agreement resulted in ICCs of 0.920 and 0.872 for the single- and multi-echo images, respectively. When the CMB counts from both raters were averaged, the multi-echo sequence detected 18.3% more CMBs than the single echo minIP SWI image (P < 0.008), with 945.5 and 798.5 total CMBs identified, respectively. Each individual patient also had more CMBs identified on the multi-echo images. These additional CMBs were typically smaller in size as shown in Figure 6B. Figure 6Open in figure viewerPowerPoint Benefits from using the multi-echo sequence. A: The multi-echo sequence allows arteries from TOF-MRA images (maxIP over 8 mm) to be overlaid on CMBs and veins from minIP SWI images without the need for registration. From the overlaid image (zoomed in to a local region specified by the dashed-box on the original images) on the left column, it can be clearly seen that one CMB is arising from venous vessels (pink dashed-box) while another one appears to originate from arterioles (green dashed-box). B: minIP SWI Images from two different patients (top and bottom rows) showing CMBs (arrows) that are visualized on both single- and multi-echo images, and three additional CMBs that are only detected on multi-echo SWI (dashed-circles). Table 2. Number of CMBs Detected on minIP SWI Images From Both Single- and Multi-echo Sequences Single-echo Multi-echo Patients Rater1 Rater2 Average Rater1 Rater2 Average 1 330 317 323.5 372 364 368 2 36 26 31 44 31 37.5 3 28 11 19.5 42 29 35.5 4 35 28 31.5 53 48 50.5 5 22 10 16 30 12 21 6 83 72 77.5 99 78 88.5 7 228 224 226 271 269 270 8 70 77 73.5 75 74 74.5 Total 832 765 798.5 986 902 945.5 Discussion The heightened susceptibility contrast recently available with higher field strength scanners has greatly motivated the investigation of the clinical relevance of CMBs in neurological disorders such as CAA,12 stroke,13 Alzheimer's disease
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