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Open Access Publications from the University of California

Scholarly Works (11 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2022)

Renal diseases that involve filtration function loss are usually diagnosed through measuring estimated glomerular filtration rate (eGFR) via blood tests such as blood urea nitrogen and serum creatinine level measurements. Although these methods allow quick assessment of renal function, it does not tell the cause of function loss and lacks adequate sensitivity due to the hyperfiltration by intact nephrons. These limitations become more critical in cases that involve progressive renal function loss such as acute kidney injury (AKI)-to-chronic kidney disease (CKD) transition and chronic graft function loss after renal transplantation, in which microstructural alterations often precede the change in blood marker levels. Biopsy remains the gold standard to pick up these tissue level damages, but the procedure is invasive and prone to sampling errors. Here, the use of novel molecular magnetic resonance imaging (MRI) technique called chemical exchange saturation transfer (CEST) imaging is demonstrated for noninvasively characterizing renal pathophysiology. Specifically, urea was studied as an imaging target and contrast agent of CEST MRI, as urea is a major metabolite responsible for controlling water reabsorption in the kidneys. Characterization of urea showed concentration and pH-dependent CEST contrast, and the feasibility of in vivo urea imaging was demonstrated with heightened CEST contrast in the inner medulla and papilla of the mouse kidneys after urea infusion. This method was further optimized for better quantification of urea by choosing the optimal time point of acquiring CEST data after urea infusion, removing T1 time effect on the CEST contrast and adopting multi-pool Lorentzian fitting. Lastly, this technique was applied to mouse renal disease models to test its diagnostic potential. Acute and chronic nephropathies were induced in mice, and the CEST data were longitudinally acquired along the disease progression. Since CEST data also reflects the presence of other mobile proteins, metabolites, and semi-solid macromolecules, the CEST contrast from these molecules were also analyzed in addition to urea. The urea CEST showed significant changes upon acute injury development, and the multiparametric CEST clearly distinguished acute and chronic nephropathies. Overall, CEST MRI can observe urea recycling in the mouse kidneys, and allows distinguishing different nephropathies along with other endogenous CEST contrast.

    Cover page: Molecular MRI Approaches for Noninvasively Characterizing Renal Pathophysiology
    • Peer Reviewed
    UC San Diego Previously Published Works (2023)
      Cover page: Quantitative Ultrashort Echo Time Magnetic Resonance Imaging: T1ρ
      • Peer Reviewed
      UC San Diego Previously Published Works (2023)
        Cover page: UTE Diffusion-Weighted Imaging (UTE-DWI)
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2024)
          Cover page: E006 Ultrashort echo time magnetic resonance imaging of myelin and iron in Huntington’s disease (HD)
          • Peer Reviewed
          UC San Diego Previously Published Works (2023)
            Cover page: Ramped Hybrid Encoding
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2024)

            Objective

            To assess and improve the reliability of the ultrashort echo time quantitative magnetization transfer (UTE-qMT) modeling of the cortical bone.

            Materials and methods

            Simulation-based digital phantoms were created that mimic the UTE-qMT properties of cortical bones. A wide range of SNR from 25 to 200 was simulated by adding different levels of noise to the synthesized MT-weighted images to assess the effect of SNR on UTE-qMT fitting results. Tensor-based denoising algorithm was applied to improve the fitting results. These results from digital phantom studies were validated via ex vivo rat leg bone scans.

            Results

            The selection of initial points for nonlinear fitting and the number of data points tested for qMT analysis have minimal effect on the fitting result. Magnetization exchange rate measurements are highly dependent on the SNR of raw images, which can be substantially improved with an appropriate denoising algorithm that gives similar fitting results from the raw images with an 8-fold higher SNR.

            Discussion

            The digital phantom approach enables the assessment of the reliability of bone UTE-qMT fitting by providing the known ground truth. These findings can be utilized for optimizing the data acquisition and analysis pipeline for UTE-qMT imaging of cortical bones.
              Cover page: Towards assessing and improving the reliability of ultrashort echo time quantitative magnetization transfer (UTE-qMT) MRI of cortical bone: In silico and ex vivo study
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2024)

              Purpose

              The semisolid myelin sheath has very fast transverse relaxation and is invisible to conventional MRI sequences. UTE sequences can detect signal from myelin. The major challenge is the concurrent detection of various water components.

              Methods

              The inversion recovery (IR)-based UTE (IR-UTE) sequence employs an adiabatic inversion pulse to invert and suppress water magnetizations. TI plays a key role in water suppression, with negative water magnetizations (negative phase) before the null point and positive water magnetizations (positive phase) after the null point. A series of dual-echo IR-UTE images were acquired with different TIs to detect water phase transition. The effects of TR in phase transition and water suppression were also investigated using a relatively long TR of 500 ms and a short TR of 106 ms. The water phase transition in dual-echo IR-UTE imaging of myelin was investigated in five ex vivo and five in vivo human brains.

              Results

              An apparent phase transition was observed in the second echo at the water signal null point, where the myelin signal was selectively detected by the UTE data acquisition at the optimal TI. The water phase transition point varied significantly across the brain when the long TR of 500 ms was used, whereas the convergence of TIs was observed when the short TR of 106 ms was used.

              Conclusion

              The results suggest that the IR-UTE sequence with a short TR allows uniform inversion and nulling of water magnetizations, thereby providing volumetric imaging of myelin.
                Cover page: Water phase transition and signal nulling in 3D dual‐echo adiabatic inversion‐recovery UTE (IR‐UTE) imaging of myelin
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2024)
                Direct imaging of semi-solid lipids, such as myelin, is of great interest as a noninvasive biomarker of neurodegenerative diseases. Yet, the short T2 relaxation times of semi-solid lipid protons hamper direct detection through conventional magnetic resonance imaging (MRI) pulse sequences. In this study, we examined whether a three-dimensional ultrashort echo time (3D UTE) sequence can directly acquire signals from membrane lipids. Membrane lipids from red blood cells (RBC) were collected from commercially available blood as a general model of the myelin lipid bilayer and subjected to D2O exchange and freeze-drying for complete water removal. Sufficiently high MR signals were detected with the 3D UTE sequence, which showed an ultrashort T2* of ∼77-271 µs and a short T1 of ∼189 ms for semi-solid RBC membrane lipids. These measurements can guide designing UTE-based sequences for direct in vivo imaging of membrane lipids.
                  Cover page: Yet more evidence that non-aqueous myelin lipids can be directly imaged with ultrashort echo time (UTE) MRI on a clinical 3T scanner: a lyophilized red blood cell membrane lipid study
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2024)
                  Motivation: Increased risk of fractures in patients with type-2 diabetes mellitus (T2DM) despite higher average bone mineral density is unexplained with routine diagnostic tools like DEXA and CT. Goal(s): This study aimed to examine the feasibility of using ultrashort echo time (UTE) magnetization transfer (MT) modeling to detect the potential differences between T2DM and normal rats. Approach: The macromolecular fraction (MMF) and proton exchange rate (kab) from UTE-MT modeling on the tibial bone of Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats were compared. Results: There was a significant difference in MMF and kab measures between the two groups. Impact: The MMF and kab measures can detect potential bone alternations related to T2DM which may help to better understand the pathogenesis of T2DM bone fractures.
                    Cover page: Macromolecular fraction and magnetization exchange rate acquired with UTE-MRI differ in the tibial bone of diabetic rats: a feasibility study
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2024)

                    Background

                    Myelin water imaging (MWI) is a myelin-specific technique, which has great potential for the assessment of demyelination and remyelination. This study develops a new MWI method, which employs a short repetition time adiabatic inversion recovery (STAIR) technique in combination with a commonly used fast spin echo (FSE) sequence and provides quantification of myelin water (MW) fractions.

                    Method

                    Whole-brain MWI was performed using the short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) technique on eight healthy volunteers (mean age: 38±14 years, four-males) and seven patients with multiple sclerosis (MS) (mean age: 53.7±8.7 years, two-males) on a 3T clinical magnetic resonance imaging scanner. To facilitate the quantification of apparent myelin water fraction (aMWF), a proton density-weighted FSE was also used during the scans to allow total water imaging. The aMWF measurements of MS lesions and normal-appearing white matter (NAWM) regions in MS patients were compared with those measured in normal white matter (NWM) regions in healthy volunteers. Both the analysis of variance (ANOVA) test and paired comparison were performed for the comparison.

                    Results

                    The MW in the whole-brain was selectively imaged and quantified using the STAIR-FSE technique in all participants. MS lesions showed much lower signal intensities than NAWM in the STAIR-FSE images. ANOVA analysis revealed a significant difference in the aMWF measurements between the three groups. Moreover, the aMWF measurements in MS lesions were significantly lower than those in both NWM of healthy volunteers and NAWM of MS patients. Lower aMWF measurements in NAWM were also found in comparison with those in NWM.

                    Conclusions

                    The STAIR-FSE technique is capable of measuring aMWF values for the indirect detection of myelin loss in MS, thus facilitating clinical translation of whole brain MWI and quantification, which show great potential for the detection and evaluation of changes in myelin in the brain of patients with MS for future larger cohort studies.
                      Cover page: Myelin water quantification in multiple sclerosis using short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) imaging
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