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Open Access Publications from the University of California

Scholarly Works (24 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2017)

Heart Disease, including Coronary Artery Disease, Hypertension, and Stroke, is the number one cause of death in the United States. Coronary artery disease (CAD) or ischemic heart disease (IHD) kills over 360,000 people per year, make up for 1 in 7 deaths in the United States. In current clinical diagnosis and management of patients with suspected CAD, various noninvasive methods including personal history, stress electrocardiogram (ECG) tests, and advanced imaging techniques are normally performed in patients with intermediate risk of CAD. If any combination of the noninvasive results suggests high-risk coronary lesion(s), the patient is then suggested to undergo invasive catheterization where invasive coronary angiography (ICA) and/or fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) are performed as the final steps of a diagnostic work-up.

Studies have shown that over 50% of patients who undergo invasive catheterization were found to have non-obstructive (<50% degree stenosis) or functionally nonsignificant (FFR > 0.80) coronary lesions, resulting in unnecessary invasive procedures. This suggests that better noninvasive methods are needed to help increase the diagnostic yield for invasive catheterization. An emerging noninvasive technique based on coronary computed tomographic angiography (CTA) in combination with computational fluid dynamics simulations to measure the functional significance of a coronary lesion, FFRCT, has shown promise. However, the method requires exposure to ionizing radiation, uses an anatomical model to simulate the hemodynamic behaviors in the coronary arteries, and may be hindered by blooming artifacts caused by densely calcified plaques which could reduce the accuracy of the overall technique.

This dissertation introduces the development of a magnetic resonance (MR) based noninvasive functional assessment for the diagnosis and management of stable CAD. The developed noninvasive technique mimics the invasive FFR and iFR methods to calculate an index using pressure. The proposed noninvasive pressure measurement framework utilizes flow velocity information obtained using phase-contrast magnetic resonance imaging (PC-MRI) in conjunction with the Navier-Stokes (NS) analysis to derive a pressure gradient across the coronary lesion of interest. Validation studies of PC-MRI velocity measurements and NS derived pressure gradient measurements were assessed in a small-caliber stenotic flow phantom at different degrees of narrowing, in healthy coronary arteries, and in a pilot patient study with diseased coronary arteries. In patient studies, noninvasive pressure gradient measurements were compared with invasive FFR and iFR to evaluate the potential of the proposed method for noninvasive functional assessment in patients with stable CAD. In addition, the method was further improved using a stack-of-stars MR acquisition approach with compressed sensing image reconstruction to allow for shorter scan time, compared to Cartesian acquisition. The approach was tested in phantoms and healthy volunteers to assess feasibility.

The success of the proposed noninvasive pressure gradient measurement method discussed in this dissertation may serve as a complementary approach to current clinical diagnostic tools, providing added information to better risk-stratify and manage patients with stable CAD. In addition, the method has the potential to serve as a gatekeeper for patients who are unlikely to benefit from invasive catheterization, hence, decrease the number of unnecessary invasive procedures.

    Cover page: Noninvasive Pressure Gradient Measurement in the Coronary Arteries using Phase Contrast Magnetic Resonance Imaging
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2017)

    Purpose

    In radiation treatment planning for thoracic and abdominal tumors, 4D-MRI has shown promise in respiratory motion characterization with improved soft-tissue contrast compared to clinical standard, 4D computed tomography (4D-CT). This study aimed to further improve vessel-tissue contrast and overall image quality in 3D radial sampling-based 4D-MRI using a slab-selective (SS) excitation approach.

    Methods

    The technique was implemented in a 3D radial sampling with self-gating-based k-space sorting sequence. The SS excitation approach was compared to a non-selective (NS) approach in six cancer patients and two healthy volunteers at 3T. Improvements in vessel-tissue contrast ratio (CR) and vessel signal-to-noise ratio (SNR) were analyzed in five of the eight subjects. Image quality was visually assessed in all subjects on a 4-point scale (0: poor; 3: excellent). Tumor (patients) and pancreas (healthy) motion trajectories were compared between the two imaging approaches.

    Results

    Compared with NS-4D-MRI, SS-4D-MRI significantly improved the overall vessel-tissue CR (2.60 ± 3.97 vs. 1.03 ± 1.44, P < 0.05), SNR (63.33 ± 38.45 vs. 35.74 ± 28.59, P < 0.05), and image quality score (2.6 ± 0.5 vs. 1.4 ± 0.5, P = 0.02). Motion trajectories from the two approaches exhibited strong correlation in the superior-inferior (0.96 ± 0.06), but weaker in the anterior-posterior (0.78 ± 0.24) and medial-lateral directions (0.46 ± 0.44).

    Conclusions

    The proposed 4D-MRI with slab-selectively excited 3D radial sampling allows for improved blood SNR, vessel-tissue CR, and image quality.
      Cover page: Improved vessel–tissue contrast and image quality in 3D radial sampling‐based 4D‐MRI
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2018)

      Purpose

      There is an increased interest to determine the exchange rate using CEST to provide pH information. However, current CEST quantification methods require lengthy scan times and do not address magnetization transfer effects. The purpose of this work was to apply the magnetic resonance fingerprinting (MRF) concept to CEST to achieve more efficient and accurate exchange rate quantification.

      Methods

      The proposed CEST fingerprinting method used varying saturation powers and saturation times to create unique signal evolutions for different exchange rates. The acquired signal was matched to a predefined dictionary to determine the exchange rate. The magnetization transfer effects were also addressed in the framework of CEST fingerprinting: The simulated dictionary could predict the signal curves without magnetization transfer effects, and comparing the dictionary to the acquired signals allowed the correction of the magnetization transfer effects. The CEST fingerprinting method was compared with the conventional pulsed quantitative CEST method using omega plots in the creatine phantom study.

      Results

      The CEST fingerprinting method has a significantly reduced scan time (10 minutes versus 50 minutes) while providing more accurate exchange rate quantification using literature values as the reference.

      Conclusion

      In this study, we demonstrate that CEST fingerprinting is more efficient (5 times faster) compared with pulsed quantitative CEST. It is also shown that the results of the proposed CEST fingerprinting technique are much closer to the literature values than pulsed quantitative CEST at 3 T.
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)

        Purpose

        Although three-dimensional (3D) turbo spin echo (TSE) with variable flip angles has proven to be useful for intracranial vessel wall imaging, it is associated with inadequate suppression of cerebrospinal fluid (CSF) signals and limited spatial coverage at 3 Tesla (T). This work aimed to modify the sequence and develop a protocol to achieve whole-brain, CSF-attenuated T1 -weighted vessel wall imaging.

        Methods

        Nonselective excitation and a flip-down radiofrequency pulse module were incorporated into a commercial 3D TSE sequence. A protocol based on the sequence was designed to achieve T1 -weighted vessel wall imaging with whole-brain spatial coverage, enhanced CSF-signal suppression, and isotropic 0.5-mm resolution. Human volunteer and pilot patient studies were performed to qualitatively and quantitatively demonstrate the advantages of the sequence.

        Results

        Compared with the original sequence, the modified sequence significantly improved the T1 -weighted image contrast score (2.07 ± 0.19 versus 3.00 ± 0.00, P = 0.011), vessel wall-to-CSF contrast ratio (0.14 ± 0.16 versus 0.52 ± 0.30, P = 0.007) and contrast-to-noise ratio (1.69 ± 2.18 versus 4.26 ± 2.30, P = 0.022). Significant improvement in vessel wall outer boundary sharpness was observed in several major arterial segments.

        Conclusions

        The new 3D TSE sequence allows for high-quality T1 -weighted intracranial vessel wall imaging at 3 T. It may potentially aid in depicting small arteries and revealing T1 -mediated high-signal wall abnormalities. Magn Reson Med 77:1142-1150, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
          Cover page: Whole‐brain intracranial vessel wall imaging at 3 Tesla using cerebrospinal fluid–attenuated T1‐weighted 3D turbo spin echo
          • Article
          • Peer Reviewed
          Abstract Background Polyoxin, a peptidyl nucleoside antibiotic, consists of three building blocks including a nucleoside skeleton, polyoximic acid (POIA), and carbamoylpolyoxamic acid (CPOAA), however, little is known about the “pathway redundancy” of the metabolic networks directing the CPOAA biosynthesis in the cell factories of the polyoxin producer. Results Here we report the genetic characterization of CPOAA biosynthesis with revealing a “pathway redundancy” in metabolic networks. Independent mutation of the four genes (polL-N and polP) directly resulted in the accumulation of polyoxin I, suggesting their positive roles for CPOAA biosynthesis. Moreover, the individual mutant of polN and polP also partially retains polyoxin production, suggesting the existence of the alternative homologs substituting their functional roles. Conclusions It is unveiled that argA and argB in L-arginine biosynthetic pathway contributed to the “pathway redundancy”, more interestingly, argB in S. cacaoi is indispensible for both polyoxin production and L-arginine biosynthesis. These data should provide an example for the research on the “pathway redundancy” in metabolic networks, and lay a solid foundation for targeted enhancement of polyoxin production with synthetic biology strategies.
            Cover page: Genetic dissection of the polyoxin building block-carbamoylpolyoxamic acid biosynthesis revealing the ¿pathway redundancy¿ in metabolic networks
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2019)

            Purpose

            To evaluate the accuracy and repeatability of a free-breathing, non-electrocardiogram (ECG), continuous myocardial T1 and extracellular volume (ECV) mapping technique adapted from the Multitasking framework.

            Methods

            The Multitasking framework is adapted to quantify both myocardial native T1 and ECV with a free-breathing, non-ECG, continuous acquisition T1 mapping method. We acquire interleaved high-spatial resolution image data and high-temporal resolution auxiliary data following inversion-recovery pulses at set intervals and perform low-rank tensor imaging to reconstruct images at 344 inversion times, 20 cardiac phases, and 6 respiratory phases. The accuracy and repeatability of Multitasking T1 mapping in generating native T1 and ECV maps are compared with conventional techniques in a phantom, a simulation, 12 healthy subjects, and 10 acute myocardial infarction patients.

            Results

            In phantoms, Multitasking T1 mapping correlated strongly with the gold-standard spin-echo inversion recovery (R2 = 0.99). A simulation study demonstrated that Multitasking T1 mapping has similar myocardial sharpness to the fully sampled ground truth. In vivo native T1 and ECV values from Multitasking T1 mapping agree well with conventional MOLLI values and show good repeatability for native T1 and ECV mapping for 60 seconds, 30 seconds, or 15 seconds of data. Multitasking native T1 and ECV in myocardial infarction patients correlate positively with values from MOLLI.

            Conclusion

            Multitasking T1 mapping can quantify native T1 and ECV in the myocardium with free-breathing, non-ECG, continuous scans with good image quality and good repeatability in vivo in healthy subjects, and correlation with MOLLI T1 and ECV in acute myocardial infarction patients.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2022)
              Iodine-induced cleavage at phosphorothioate DNA (PT-DNA) is characterized by extremely high sensitivity (∼1 phosphorothioate link per 106 nucleotides), which has been used for detecting and sequencing PT-DNA in bacteria. Despite its foreseeable potential for wide applications, the cleavage mechanism at the PT-modified site has not been well established, and it remains unknown as to whether or not cleavage of the bridging P-O occurs at every PT-modified site. In this work, we conducted accurate ωB97X-D calculations and high-performance liquid chromatography-mass spectrometry to investigate the process of PT-DNA cleavage at the atomic and molecular levels. We have found that iodine chemoselectively binds to the sulfur atom of the phosphorothioate link via a strong halogen-chalcogen interaction (a type of halogen bond, with binding affinity as high as 14.9 kcal/mol) and thus triggers P-O bond cleavage via phosphotriester-like hydrolysis. Additionally, aside from cleavage of the bridging P-O bond, the downstream hydrolyses lead to unwanted P-S/P-O conversions and a loss of the phosphorothioate handle. The mechanism we outline helps to explain specific selectivity at the PT-modified site but also predicts the dynamic stoichiometry of P-S and P-O bond breaking. For instance, Tris is involved in the cascade derivation of S-iodo-phosphorothioate to S-amino-phosphorothioate, suppressing the S-iodo-phosphorothioate hydrolysis to a phosphate diester. However, hydrolysis of one-third of the Tris-O-grafting phosphotriester results in unwanted P-S/P-O conversions. Our study suggests that bacterial DNA phosphorothioation may more frequently occur than previous bioinformatic estimations have predicted from iodine-induced deep sequencing data.
                Cover page: Origin of iodine preferential attack at sulfur in phosphorothioate and subsequent P-O or P-S bond dissociation
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2020)
                PURPOSE: To develop a simultaneous T1 , T2 , and ADC mapping method that provides co-registered, distortion-free images and enables multiparametric quantification of 3D brain coverage in a clinically feasible scan time with the MR Multitasking framework. METHODS: The T1 /T2 /diffusion weighting was generated by a series of T2 preparations and diffusion preparations. The underlying multidimensional image containing 3 spatial dimensions, 1 T1 weighting dimension, 1 T2 -preparation duration dimension, 1 b-value dimension, and 1 diffusion direction dimension was modeled as a 5-way low-rank tensor. A separate real-time low-rank model incorporating time-resolved phase correction was also used to compensate for both inter-shot and intra-shot phase inconsistency induced by physiological motion. The proposed method was validated on both phantom and 16 healthy subjects. The quantification of T1 /T2 /ADC was evaluated for each case. Three post-surgery brain tumor patients were scanned for demonstration of clinical feasibility. RESULTS: Multitasking T1 /T2 /ADC maps were perfectly co-registered and free from image distortion. Phantom studies showed substantial quantitative agreement ( R2=0.999 ) with reference protocols for T1 /T2 /ADC. In vivo studies showed nonsignificant T1 (P = .248), T2 (P = .97), ADC (P = .328) differences among the frontal, parietal, and occipital regions. Although Multitasking showed significant differences of T1 (P = .03), T2 (P < .001), and ADC (P = .001) biases against the references, the mean bias estimates were small (ΔT1 % < 5%, ΔT2 % < 7%, ΔADC% < 5%), with all intraclass correlation coefficients greater than 0.82 indicating excellent agreement. Patient studies showed that Multitasking T1 /T2 /ADC maps were consistent with the clinical qualitative images. CONCLUSION: The Multitasking approach simultaneously quantifies T1 /T2 /ADC with substantial agreement with the references and is promising for clinical applications.
                  Cover page: Three-dimensional simultaneous brain T1 , T2 , and ADC mapping with MR Multitasking.
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2015)

                  Purpose

                  To apply a novel self-gating k-space sorted 4-dimensional MRI (SG-KS-4D-MRI) method to overcome limitations due to anisotropic resolution and rebinning artifacts and to monitor pancreatic tumor motion.

                  Methods and materials

                  Ten patients were imaged using 4D-CT, cine 2-dimensional MRI (2D-MRI), and the SG-KS-4D-MRI, which is a spoiled gradient recalled echo sequence with 3-dimensional radial-sampling k-space projections and 1-dimensional projection-based self-gating. Tumor volumes were defined on all phases in both 4D-MRI and 4D-CT and then compared.

                  Results

                  An isotropic resolution of 1.56 mm was achieved in the SG-KS-4D-MRI images, which showed superior soft-tissue contrast to 4D-CT and appeared to be free of stitching artifacts. The tumor motion trajectory cross-correlations (mean ± SD) between SG-KS-4D-MRI and cine 2D-MRI in superior-inferior, anterior-posterior, and medial-lateral directions were 0.93 ± 0.03, 0.83 ± 0.10, and 0.74 ± 0.18, respectively. The tumor motion trajectories cross-correlations between SG-KS-4D-MRI and 4D-CT in superior-inferior, anterior-posterior, and medial-lateral directions were 0.91 ± 0.06, 0.72 ± 0.16, and 0.44 ± 0.24, respectively. The average standard deviation of gross tumor volume calculated from the 10 breathing phases was 0.81 cm(3) and 1.02 cm(3) for SG-KS-4D-MRI and 4D-CT, respectively (P=.012).

                  Conclusions

                  A novel SG-KS-4D-MRI acquisition method capable of reconstructing rebinning artifact-free, high-resolution 4D-MRI images was used to quantify pancreas tumor motion. The resultant pancreatic tumor motion trajectories agreed well with 2D-cine-MRI and 4D-CT. The pancreatic tumor volumes shown in the different phases for the SG-KS-4D-MRI were statistically significantly more consistent than those in the 4D-CT.
                    Cover page: Four-Dimensional Magnetic Resonance Imaging&nbsp;With 3-Dimensional Radial Sampling and Self-Gating–Based K-Space Sorting: Early Clinical Experience on Pancreatic Cancer Patients
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2017)
                    BACKGROUND:Previous studies have linked cardiac dysfunction to loss of metabolites in the creatine kinase system. Chemical exchange saturation transfer (CEST) is a promising metabolic cardiovascular magnetic resonance (CMR) imaging technique and has been applied in the heart for creatine mapping. However, current limitations include: (a) long scan time, (b) residual cardiac and respiratory motion, and (c) B0 field variations induced by respiratory motion. An improved CEST CMR technique was developed to address these problems. METHODS:Animals with chronic myocardial infarction (N = 15) were scanned using the proposed CEST CMR technique and a late gadolinium enhancement (LGE)  sequence as reference. The major improvements of the CEST CMR technique are: (a) Images were acquired by single-shot FLASH, significantly increasing the scan efficiency. (b) All images were registered to reduce the residual motion. (c) The acquired Z-spectrum was analyzed using 3-pool-model Lorentzian-line fitting to generate CEST signal, reducing the impact of B0 field shifting due to respiratory motion. Feasibility of the technique was tested in a porcine model with chronic myocardial infarction. CEST signal was measured in the scar, border zone and remote myocardium. Initial studies were performed in one patient. RESULTS:In all animals, healthy remote myocardial CEST signal was elevated (0.16 ± 0.02) compared to infarct CEST signal (0.09 ± 0.02, P < 0.001) and the border zone (0.12 ± 0.02, P < 0.001). For both animal and patient studies, the hypointense regions in the CEST contrast maps closely match the bright areas in the LGE images. CONCLUSIONS:The proposed CEST CMR technique was developed to address long scan times, respiratory and cardiac motion, and B0 field variations. Lower CEST signal in bright region of the LGE image is consistent with the fact that myocardial infarction has reduced metabolic activity.
                      Cover page: Optimized CEST cardiovascular magnetic resonance for assessment of metabolic activity in the heart
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