Ali Hariri

Characterization of Skn-1a/i POU Domain Factors and Linkage to Papillomavirus Gene Expression

Tissue-restricted POU domain transcription factors, which bind octamer or octamer-like gene sequences, play roles in cellular differentiation and the development of several organs. We have previously identified a POU domain gene, Skn-1a/i, expressed primarily in epidermis, that encodes at least two products through alternative splicing. One of these, Skn-1a, acts as a transcriptional activator, and the other, Skn-1i, contains an inhibitory domain in the NH2 terminus, which prevents DNA-binding in vitro and transcriptional activationin vivo. We now demonstrate that when Skn-1i is expressed in eukaryotic cells it can bind to an octamer site, suggesting thatin vivo cellular factors modulate the activity of the inhibitory domain to permit DNA-binding. Yet the inhibitory domain does not allow transactivation by Skn-1i or by a heterologous transactivator containing this domain in cis. Furthermore, we demonstrate that Skn-1a, Tst-1, and Oct-1 are the major octamer-binding proteins in epidermis. Since Skn-1a is primarily expressed in suprabasal cells of the epidermis, we have tested its possible role in the regulation of epidermal papillomaviruses. In transient transfection assays, Skn-1a and Tst-1 can activate the long control region of the epidermis-specific human papillomavirus 1A (HPV-1A). Consistent with these in vivo transcription data, in vitro DNA binding studies identify three octamer-like sites, which are capable of binding Skn-1a, in the HPV-1A long control region. Mutations of all three octamer-like sites prevent transactivation by Skn-1a in transient transfection assays. Taken together, these results provide evidence that Skn-1a and Tst-1 may provide a molecular link between HPV gene expression and epidermal differentiation.

The characterization of an economic and portable LED-based photoacoustic imaging system to facilitate molecular imaging

Graphical abstract

Development of low-cost photoacoustic imaging systems using very low-energy pulsed laser diodes

Abstract. With the growing application of photoacoustic imaging (PAI) in medical fields, there is a need to make them more compact, portable, and affordable. Therefore, we designed very low-cost PAI systems by replacing the expensive and sophisticated laser with a very low-energy laser diode. We implemented photoacoustic (PA) microscopy, both reflection and transmission modes, as well as PA computed tomography systems. The images obtained from tissue-mimicking phantoms and biological samples determine the feasibility of using a very low-energy laser diode in these configurations.

Photoacoustic Imaging for Noninvasive Periodontal Probing Depth Measurements

The periodontal probe is the gold standard tool for periodontal examinations, including probing depth measurements, but is limited by systematic and random errors. Here, we used photoacoustic ultrasound for high–spatial resolution imaging of probing depths. Specific contrast from dental pockets was achieved with food-grade cuttlefish ink as a contrast medium. Here, 39 porcine teeth (12 teeth with artificially deeper pockets) were treated with the contrast agent, and the probing depths were measured with novel photoacoustic imaging and a Williams periodontal probe. There were statistically significant differences between the 2 measurement approaches for distal, lingual, and buccal sites but not mesial. Bland-Altman analysis revealed that all bias values were < ±0.25 mm, and the coefficients of variation for 5 replicates were <11%. The photoacoustic imaging approach also offered 0.01-mm precision and could cover the entire pocket, as opposed to the probe-based approach, which is limited to only a few sites. This report is the first to use photoacoustic imaging for probing depth measurements with potential implications to the dental field, including tools for automated dental examinations or noninvasive examinations.

Transcranial DC stimulation modifies functional connectivity of large-scale brain networks in abstinent methamphetamine users

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool suited to alter cortical excitability and activity via the application of weak direct electrical currents. An increasing number of studies in the addiction literature suggests that tDCS modulates subjective self‐reported craving through stimulation of dorsolateral prefrontal cortex (DLPFC). The major goal of this study was to explore effects of bilateral DLPFC stimulation on resting state networks (RSNs) in association with drug craving modulation. We targeted three large‐scale RSNs; the default mode network (DMN), the executive control network (ECN), and the salience network (SN).

Enhanced Performance of a Molecular Photoacoustic Imaging Agent by Encapsulation in Mesoporous Silicon Nanoparticles

Photoacoustic (PA) imaging allows visualization of the physiology and pathology of tissues with good spatial resolution and relatively deep tissue penetration. The method converts near-infrared (NIR) laser excitation into thermal expansion, generating pressure transients that are detected with an acoustic transducer. Here, we find that the response of the PA contrast agent indocyanine green (ICG) can be enhanced 17-fold when it is sealed within a rigid nanoparticle. ICG encapsulated in particles composed of porous silicon (pSiNP), porous silica, or calcium silicate all show greater PA contrast relative to equivalent quantities of free ICG, with the pSiNPs showing the strongest enhancement. A liposomal formulation of ICG performs similar to free ICG, suggesting that a rigid host nanostructure is necessary to enhance ICG performance. The improved response of the nanoparticle formulations is attributed to the low thermal conductivity of the porous inorganic hosts and their ability to protect the ICG payload from photolytic and/or thermal degradation. The translational potential of ICG-loaded pSiNPs as photoacoustic probes is demonstrated via imaging of a whole mouse brain.

Photoacoustic Signal Enhancement: Towards Utilization of Low Energy Laser Diodes in Real-Time Photoacoustic Imaging

In practice, photoacoustic (PA) waves generated with cost-effective and low-energy laser diodes, are weak and almost buried in noise. Reconstruction of an artifact-free PA image from noisy measurements requires an effective denoising technique. Averaging is widely used to increase the signal-to-noise ratio (SNR) of PA signals; however, it is time consuming and in the case of very low SNR signals, hundreds to thousands of data acquisition epochs are needed. In this study, we explored the feasibility of using an adaptive and time-efficient filtering method to improve the SNR of PA signals. Our results show that the proposed method increases the SNR of PA signals more efficiently and with much fewer acquisitions, compared to common averaging techniques. Consequently, PA imaging is conducted considerably faster.

A portable and economical LED-based photoacoustic imaging system for molecular imaging (Conference Presentation)

We characterized a commercially available LED-based photoacoustic system (Prexion Inc. Japan) that offered a tunable LED pulse repetition rate (1K Hz, 2K Hz, 3K Hz, and 4K Hz) and found that the temporal resolution of the scanner is dependent on the choice of repetition rate. The LED system have lower power, and averaging is used to minimize the noise. The power from the LED arrays at 690 nm and 850 nm with 70 ns pulse width was measured to be 9.85 mW/cm2 and 31.55 mW/cm2. Beam profiling showed that the average intensity at the center of the transducer was ~ 18% higher than the power on the edges of the transducer. The system had axial and lateral resolution of 268 μm and 590 μm, respectively. This system has frame rates of 30 Hz and 0.15 Hz. Pencil lead inside chicken breast could be detected up to 3.2 cm deep with a frame rate of 15 Hz. Indocyanine green (ICG), methylene blue (MB), and DiR were used as exogenous contrasts to measure the limit of detection using PLED-PAI. The limit of detection values for ICG, MB, and DiR are 9 μM, 0.75 mM, and 68 μM, respectively. For in vivo experiments, DiR (positive control), 400,000 stem cells labeled with DiR, and bare stem cells (negative control) were subcutaneously injected on the spinal cord of male mice. Results shows difference between labeled and unlabeled cells in photoacoustic intensity using PLED-PAI. This experiment shows the capability of this LED-based system to perform molecular imaging at a price point and device footprint nearly a log order smaller than systems based on an optical parametric oscillator laser.

A photoacoustic imaging approach using food grade contrast agent for pocket depth measurements (Conference Presentation)

Periodontal probing is a useful diagnostic tool to estimate the periodontal pocket depth and assess the status of periodontal disease, but is limited by systematic and random errors. Here, we used photoacoustic imaging in tandem with a food grade cuttlefish ink contrast agent to specifically measure pocket depths in swine models (n=27 teeth) and then compared this to Williams probe. Photoacoustic imaging used a Vevo LAZR imaging system (Visualsonics) at 40 MHz. Spectral data was collected at both 680 and 800 nm to discriminate between the photoacoustic signal from stains and contrast agent. The pocket depths were measured on the sagittal view of the 3D images as well as with a Williams probe before photoacoustic imaging. The Bland-Altman plots show that 97% of our samples fell within ± 1.96 standard deviations of the differences between the depths measured by photoacoustic imaging and the probe (95% confidence interval) at mesial, lingual and buccal, and distal locations. Small bias values of -0.04, +0.17, and -0.2 mm were identified at mesial, lingual and buccal, and distal locations, respectively; the 95% confidence intervals are plotted as well and all are < 1.0 mm. The photoacoustic imaging approach also offered 0.01 mm precision and could cover the entire pocket versus the probe-based approach that is limited to only a few sites.

The double-stage delay-multiply-and-sum image reconstruction method improves imaging quality in a LED-based photoacoustic array scanner

Light-emitting diode-based photoacoustic imaging is more compact and affordable than laser-based systems, but it has low power and hence a high number of replicates. Here, we describe double-stage delay-multiply-and-sum (DS-DMAS) to improve image quality collected on a LED-based scanner. DS-DMAS was evaluated experimentally using point targets (in different laterals and depths) as well as a hair and a rabbit eye. This algorithm can compensate for the low SNR of LED-based systems and offer better lateral resolution of about 60%, 25%, higher contrast ratio of about 97%, 34%, and better full-width-half-maximum of about 60%, 25%, versus delay-and-sum) and delay-multiply-and-sum, respectively. More importantly, DS-DMAS offers this using a smaller number of frames (only 2% of all the frames). These results indicate that DS-DMAS might be a valuable tool in the translation of LED-based and other low power PAI systems.