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The Value of First-Order Features Based on the Apparent Diffusion Coefficient Map in Evaluating the Therapeutic Effect of Low-Intensity Pulsed Ultrasound for Acute Traumatic Brain Injury With a Rat Model

Dan Du, Yajuan Gao, Tao Zheng, Linsha Yang, Zhanqiu Wang, Qinglei Shi, Shuo Wu, Xin Liang, Xinyu Yao, Jiabin Lu, Lanxiang Liu

Frontiers in Computational Neuroscience 2022 · 10.3389/fncom.2022.923247

rodenttraumatic brain injuryother mrihistology molecular

Abstract

Purpose In order to evaluate the neuroprotective effect of low-intensity pulsed ultrasound (LIPUS) for acute traumatic brain injury (TBI), we studied the potential of apparent diffusion coefficient (ADC) values and ADC-derived first-order features regarding this problem. Methods Forty-five male Sprague Dawley rats (sham group: 15, TBI group: 15, LIPUS treated: 15) were enrolled and underwent magnetic resonance imaging. Scanning layers were acquired using a multi-shot readout segmentation of long variable echo trains (RESOLVE) to decrease distortion. The ultrasound transducer was applied to the designated region in the injured cortical areas using a conical collimator and was filled with an ultrasound coupling gel. Regions of interest were manually delineated in the center of the damaged cortex on the diffusion weighted images ( b = 800 s/mm 2 ) layer by layer for the TBI and LIPUS treated groups using the open-source software ITK-SNAP. Before analysis and modeling, the features were normalized using a z-score method, and a logistic regression model with a backward filtering method was employed to perform the modeling. The entire process was completed using the R language. Results During the observation time, the ADC values ipsilateral to the trauma in the TBI and LIPUS groups increased rapidly up to 24 h. After statistical analysis, the 10th percentile, 90th percentile, mean, skewness, and uniformity demonstrated a significant difference among three groups. The receiver operating characteristic curve (ROC) analysis shows that the combined LR model exhibited the highest area under the curve value (AUC: 0.96). Conclusion The combined LR model of first-order features based on the ADC map can acquire a higher diagnostic performance than each feature only in evaluating the neuroprotective effect of LIPUS for TBI. Models based on first-order features may have potential value in predicting the therapeutic effect of LIPUS in clinical practice in the future.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects15 animals
Sessions per subject7
Randomisedyes
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsother mri, histology molecular — DWI/ADC map first-order features (RESOLVE); GFAP immunohistochemistry
Direction of effectnot assessedADC values ipsilateral to trauma peaked lower in the LIPUS group than the TBI group at 24 h and were lower and closer to sham at 7 d; interpreted as neuroprotection.
Adverse eventsnot reported

Exposures

Exposure 1: LIPUS to injured cortex

Target: cerebral cortex — “designated region in the injured cortical areas”
Device: Olympus / Panametrics · Olympus · V301-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)0.5✓✓✓
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 50%⚑
Sonication duration (s)0.4✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Isppa, domain unspecified (W/cm²)2.6✓✓✓⚑
Protocol, in the paper’s words

Unfocused transducer with conical collimator (10 mm) and coupling gel; total stimulation duration 10 min, once per day for 7 days, started immediately after CCI. Stimulation duration 400 ms, tone-burst duration 0.5 ms, PRF 1 kHz.

Flags from extraction

  • exposures[0].unspecified_domain.isppa_w_cm2 — Isppa measured with a needle hydrophone, but the paper does not say water or free field; kept unspecified.
  • exposures[0].timing.duty_cycle_pct — Duty cycle not stated; not computed.
  • exposures[0].timing.sonication_duration_s — 400 ms 'stimulation duration' per train, with total stimulation 10 min; read as the train length.
  • n_subjects — 45 rats enrolled in total (sham 15, TBI 15, LIPUS 15); only the 15 LIPUS rats received ultrasound.
  • blinding — Only GFAP scoring was by blinded observers; no overall blinding statement.