Spectroscopic Photoacoustic Imaging for Accessing Cervical Tissue Composition in Human Cervical Biopsies

Author(s):  
Yan Yan ◽  
Maryam Basij ◽  
Alpana Garg ◽  
Aneesha Varrey ◽  
Ali Alhousseini ◽  
...  
PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247385
Author(s):  
Yan Yan ◽  
Maryam Basij ◽  
Alpana Garg ◽  
Aneesha Varrey ◽  
Ali Alhousseini ◽  
...  

Objective Cervical remodeling is an important component in determining the pathway of parturition; therefore, assessing changes in cervical tissue composition may provide information about the cervix’s status beyond the measurement of cervical length. Photoacoustic imaging is a non-invasive ultrasound-based technology that captures acoustic signals emitted by tissue components in response to laser pulses. This optical information allows for the determination of the collagen-to-water ratio (CWR). The purpose of this study was to compare the CWR evaluated by using spectroscopic photoacoustic (sPA) imaging in cervical samples obtained from pregnant and non-pregnant women. Methods This cross-sectional study comprised cervical biopsies obtained at the time of hysterectomy (n = 8) and at the scheduled cesarean delivery in pregnant women at term who were not in labor (n = 8). The cervical CWR was analyzed using a fiber-optic light-delivery system integrated to an ultrasound probe. The photoacoustic signals were acquired within the range of wavelengths that cover the peak absorption of collagen and water. Differences in the CWR between cervical samples from pregnant and non-pregnant women were analyzed. Hematoxylin and eosin and Sirius Red stains were used to compare the collagen content of cervical samples in these two groups. Results Eight cervix samples were obtained after hysterectomy, four from women ≤41 years of age and four from women ≥43 years of age; all cervical samples (n = 8) from pregnant women were obtained after 37 weeks of gestation at the time of cesarean section. The average CWR in cervical tissue samples from pregnant women was 18.7% (SD 7.5%), while in samples from non-pregnant women, it was 55.0% (SD 20.3%). There was a significantly higher CWR in the non-pregnant group compared to the pregnant group with a p-value <0.001. A subgroup analysis that compared the CWR in cervical samples from pregnant women and non-pregnant women ≤41 years of age (mean 46.3%, SD 23.1%) also showed a significantly higher CWR (p <0.01). Lower collagen content in the pregnancy group was confirmed by histological analysis, which revealed the loss of tissue composition, increased water content, and collagen degradation. Conclusion The proposed bimodal ultrasound and sPA imaging system can provide information on the biochemical composition of cervical tissue in pregnant and non-pregnant women. Photoacoustic imaging showed a higher collagen content in cervical samples from non-pregnant women as compared to those from pregnant women, which matched with the histological analysis. This novel imaging method envisions a new potential for a sensitive diagnostic tool in the evaluation of cervical tissue composition.


2019 ◽  
Vol 220 (1) ◽  
pp. S14-S15 ◽  
Author(s):  
Aneesha Varrey ◽  
Mohammad Mehrmohammadi ◽  
Alpana Garg ◽  
Faisal Qureshi ◽  
Yan Yan ◽  
...  

2020 ◽  
Author(s):  
Lungwani Muungo

Objectives: Self-administered vaginal rings are a promising method for delivery of topical anti-HIV microbicidesand might offer an adherence advantage over daily or coitally-dependent dosage forms such as gels. This trialassessed the safety and pharmacokinetic aspects of the Dapivirine Vaginal Ring-004 when worn as multiple rings oversequential periods of ring use by healthy, sexually-active, HIV-negative women.Methods: This double-blind trial was conducted among 48 women (18-40 years). Participants were randomlyassigned to two groups (A or B) and received (3:1) either the dapivirine or a placebo vaginal ring. Group A used tworings over a 56-day period and Group B used three rings over a 57-day period. Safety evaluations were conductedthroughout the trial. Dapivirine concentrations were measured in plasma, vaginal fluid and cervical tissue samplescollected during and after the 56 days (Group A) or 57 days (Group B) of vaginal ring use.Results: Ring-004 was safe and well tolerated in all participants. The pharmacokinetic profile demonstrated arapid increase in plasma and vaginal fluid concentrations and achieved concentrations in vaginal fluids and cervicaltissue well above the in vitro IC99 in cervical tissue (3.3 ng/mL) that were sustained for a 28 to 35-day ring use period(approximately 3000 times higher in vaginal fluids and 14 -1000 times higher in cervical tissue). Drug levels wereassociated with significant inhibitory activity of genital secretions against HIV ex vivo, a biomarker of pharmacodynamics.Individual plasma dapivirine concentrations did not exceed 553 pg/mL and were well below plasma concentrations atthe maximum tolerated dose for oral treatment (mean Cmax 2286 ng/mL).Conclusions: The consecutive use of several rings over a period of up to 57 days was safe and well tolerated, andPK data indicate that a single Ring-004 is likely to be protective for at least 35 days.


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