Biology subjects

Perlman, O.

Publications and source records attributed to Perlman, O..

4 recordsLinked to original sources

bioRxiv2026

Quantitative Semisolid Magnetization Transfer and Relayed Nuclear Overhauser Effect Imaging in a Multiple Sclerosis Mouse Model Using Deep Magnetic Resonance Fingerprinting

Magnetic resonance imaging (MRI) is the imaging modality of choice for the diagnosis, characterization, and monitoring of multiple sclerosis (MS). Nevertheless, the contrasts manifested by MS lesions often overlap with those of other pathological conditions, highlighting the need for additional disease biomarkers. In addition, while saturation transfer (ST) MRI provides molecular information associated with myelin, protein, and lipids, quantifying the underlying proton exchange parameters remains challenging. Here, we describe a strategy that extends and modifies AI-boosted ST magnetic resonance fingerprinting (MRF) imaging at 7T. This approach was used to quantify the dynamics of the semisolid magnetization transfer (MT) and the aliphatic relayed nuclear Overhauser effect (rNOE at -3.5 ppm and -1.6 ppm relative to water) in a longitudinal cuprizone MS mouse model (n=12). In lipid phantoms, the reconstructed proton volume fractions were strongly correlated with known lipid concentrations across all three proton pools (r>0.96, p<0.001). In vivo, semisolid MT and rNOE proton volume fractions in the corpus callosum demonstrated a significant decrease (p<0.01) as early as week 4 of cuprizone feeding, preceding changes detected by conventional water relaxometry. ST-MRF based biomarkers were in agreement with histological findings. Overall, our results demonstrate the feasibility of rapid, multi-pool ST-MRF quantification for MS characterization.

bioengineering↗

bioRxiv2022

Protein Optimization Evolving Tool (POET) based on Genetic Programming

Proteins are used by scientists to serve a variety of purposes in clinical practice and laboratory research. To optimize proteins for greater function, a variety of techniques have been developed. For the development of reporter genes used in Magnetic Resonance Imaging (MRI) based on Chemical Exchange Saturation Transfer (CEST), these techniques have encountered a variety of challenges. Here we develop a mechanism of protein optimization using a computational approach known as "genetic programming". We developed an algorithm called Protein Optimization Evolving Tool (POET). Starting from a small library of literature values, use of this tool allowed us to develop proteins which produce four times more MRI contrast than what was previously state-of-the-art. Next, we used POET to evolve peptides that produced CEST-MRI contrast at large chemical shifts where no other known peptides have previously demonstrated contrast. This demonstrated the ability of POET to evolve new functions in proteins. Interestingly, many of the peptides produced using POET were dramatically different with respect to their sequence and chemical environment than existing CEST producing peptides, and challenge prior understandings of how those peptides function. This suggests that unlike existing algorithms for protein engineering that rely on divergent evolution, POET relies on convergent evolution.

synthetic biology↗

bioRxiv2020

Redesigned Reporter Gene for Improved Proton Exchange-based Molecular MRI Contrast

Reporter gene imaging allows for non-invasive monitoring of molecular processes in living cells, providing insights on the mechanisms underlying pathology and therapy. A lysine-rich protein (LRP) chemical exchange saturation transfer (CEST) MRI reporter gene has previously been developed and used to image tumor cells, cardiac viral gene transfer, and oncolytic virotherapy. However, the highly repetitive nature of the LRP reporter gene sequence leads to DNA recombination events and the expression of a range of truncated LRP protein fragments, thereby greatly limiting the CEST sensitivity. Here we report the use of a redesigned LRP reporter (rdLRP), aimed to provide excellent stability and CEST sensitivity. The rdLRP contains no DNA repeats or GC rich regions and 30% less positively charged amino-acids. RT-PCR of cell lysates transfected with rdLRP demonstrated a stable reporter gene with a single distinct band corresponding to full-length DNA. A distinct increase in CEST-MRI contrast was obtained in cell lysates of rdLRP transfected cells and in in vivo LRP expressing mouse brain tumors (p=0.0275, n=10).

bioengineering↗

bioRxiv2020

AI boosted molecular MRI for apoptosis detection in oncolytic virotherapy

Oncolytic virotherapy is a promising treatment for high mortality cancers1. Non-invasive imaging of the underlying molecular processes is an essential tool for therapy optimization and assessment of viral spread, innate immunity, and therapeutic response2, 3. However, previous methods for imaging oncolytic viruses did not correlate with late viral activity4 or had poor sensitivity and specificity5. Similarly, methods developed to image treatment response, such as apoptosis, proved to be slow, nonspecific, or require the use of radioactive or metal-based contrast agents6-8. To date, no method has been widely adopted for clinical use. We describe here a new method for fast magnetic resonance molecular imaging with quantitative proton chemical-exchange specificity to monitor oncolytic virotherapy treatment response. A deep neural network enabled the computation of quantitative biomarker maps of protein and lipid/macromolecule concentrations as well as intracellular pH in a glioblastoma multiforme mouse brain tumor model. Early detection of apoptotic response to oncolytic virotherapy, characterized by decreased cytosolic pH and protein synthesis, was observed in agreement with histology. Clinical translation was demonstrated in a normal human subject, yielding molecular parameters in good agreement with literature values9. The developed method is directly applicable to a wide range of pathologies, including stroke10, cancer11-13, and neurological disorders14, 15.

biophysics↗