ABSTRACT
Intravascular ultrasound (IVUS) imaging catheters are significant tools for cardiovascular interventions, and their use can be expanded by realizing IVUS imaging guidewires and microcatheters. The miniaturization of these devices creates challenges in SNR due to the need for higher frequencies to provide adequate resolution. An integrated IVUS system with transmit beamforming can mitigate these limitations. This work presents the first practical highly integrated system-on-a-chip (SoC) with plane wave transmit beamforming at 40 MHz for IVUS on guidewire or microcatheters. The front-end circuitry has a 20-channel ultrasound transmitter (Tx) and receiver (Rx) array interfaced with a capacitive micromachined ultrasound transducer (CMUT) array. During each firing, all 20 Tx are excited with the same analog delay with respect to each other, which can be continuously adjusted between ~0 and 10 ns in two directions, generating a steerable plane wave in a range of ±/-50° for a phased array at 40 MHz. The unit delays are generated via a voltage-controlled delay line (VCDL), which only needs two external controls, one tuning the unit delay and the other determining the steering direction. The SoC is fabricated using a 180-nm high-voltage (HV) CMOS process and features a slender active area of 0.3 mm × 3.7 mm. The proposed SoC consumes 31.3 mW during the receiving mode. The beamformer's functionality and the SoC's overall performance were validated through acoustic characterization and imaging experiments.
ABSTRACT
Lengthy trinucleotide repeats encoding polyglutamine (polyQ) stretches characterize the variant proteins of Huntington's disease and certain other inherited neurological disorders. Using a phenotypic screen to identify events that restore functionality to polyQ proteins in S. cerevisiae, we discovered that transcription elongation factor Spt4 is required to transcribe long trinucleotide repeats located either in ORFs or nonprotein-coding regions of DNA templates. Mutation of SPT4 selectively decreased synthesis of and restored enzymatic activity to expanded polyQ protein without affecting protein lacking long-polyQ stretches. RNA-seq analysis revealed limited effects of Spt4 on overall gene expression. Inhibition of Supt4h, the mammalian ortholog of Spt4, reduced mutant huntingtin protein in neuronal cells and decreased its aggregation and toxicity while not altering overall cellular mRNA synthesis. Our findings identify a cellular mechanism for transcription through repeated trinucleotides and a potential target for countermeasures against neurological disorders attributable to expanded trinucleotide regions.
