Charles Alexander Mosse

A laser scanning system for the measurement of facial surface morphology

Abstract A no contact system based on laser scanning, which records 20 000 facial surface coordinates with a dynamic resolution of approximately 0·9mm in 30s, has been developed for the study of facial changes following facial reconstructive surgery. Individual profiles are recorded with a resolution better than 0·5mm. The system is based on the analysis of the output from a video camera which obliquely views a laser line projected vertically onto the face. In order to sample the whole face, the subject sits on a chair which rotates at six degrees per second under computer control. Examples of applications of the system are given.

A Microchannel Neuroprosthesis for Bladder Control After Spinal Cord Injury in Rat

An electronic interface for recording and stimulating nerves that innervate the bladder helps to restore normal bladder function in rats with spinal cord injury. Getting to the Root of Bladder Control Injury to the spinal cord typically results in loss of conscious bladder emptying and the sensation of fullness. Currently, only limited treatment options are available, with most of the patients receiving catheterization. However, this is cumbersome and leads to urological complications including unsolicited episodes of bladder contraction, leading to inappropriate emptying. In a new study, Chew et al. design a “closed-loop” electronic device that can accurately record bladder filling from sensory nerves after spinal cord injury in rat. Using this information, bladder emptying can be artificially stimulated on demand by electrically modulating nerve firing. It is traditionally difficult to record robust neuronal activity from peripheral nerves in vivo. Typically, cuff electrodes are used to record from whole nerves, but produce poor signal quality and provide little indication of bladder filling. Through nerve microdissection, Chew et al. implanted fine-diameter nerves (“rootlets”) into insulated microchannels, recording action potential firing that accurately encoded bladder filling. The device had multiple microchannels for concurrent recording, greatly improving the resolution. Using this sensory information and by manipulating stimulation characteristics, the authors prevented the rat bladder from emptying inappropriately, and bladder contraction was initiated when desired. This work opens a new avenue for the design of a neuroprosthesis for bladder control after spinal cord injury. A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness. We designed a closed-loop neuroprosthetic interface that measures bladder fullness and prevents spontaneous voiding episodes without the need for dorsal rhizotomy in a rat model. To obtain bladder sensory information, we implanted teased dorsal roots (rootlets) within the rat vertebral column into microchannel electrodes, which provided signal amplification and noise suppression. As long as they were attached to the spinal cord, these rootlets survived for up to 3 months and contained axons and blood vessels. Electrophysiological recordings showed that half of the rootlets propagated action potentials, with firing frequency correlated to bladder fullness. When the bladder became full enough to initiate spontaneous voiding, high-frequency/amplitude sensory activity was detected. Voiding was abolished using a high-frequency depolarizing block to the ventral roots. A ventral root stimulator initiated bladder emptying at low frequency and prevented unwanted contraction at high frequency. These data suggest that sensory information from the dorsal root together with a ventral root stimulator could form the basis for a closed-loop bladder neuroprosthetic.

Laser-generated ultrasound with optical fibres using functionalised carbon nanotube composite coatings

Optical ultrasound transducers were created by coating optical fibres with a composite of carbon nanotubes (CNTs) and polydimethylsiloxane (PDMS). Dissolution of CNTs in PDMS to create the composite was facilitated by functionalisation with oleylamine. Composite surfaces were applied to optical fibres using dip coating. Under pulsed laser excitation, ultrasound pressures of 3.6 MPa and 4.5 MPa at the coated end faces were achieved with optical fibre core diameters of 105 and 200 μm, respectively. The results indicate that CNT-PDMS composite coatings on optical fibres could be viable alternatives to electrical ultrasound transducers in miniature ultrasound imaging probes.

Image cytometry accurately detects DNA ploidy abnormalities and predicts late relapse to high-grade dysplasia and adenocarcinoma in Barrett's oesophagus following photodynamic therapy

Background and aims:DNA ploidy abnormalities (aneuploidy/tetraploidy) measured by flow cytometry (FC) are strong predictors of future cancer development in untreated Barretts oesophagus, independent of histology grade. Image cytometric DNA analysis (ICDA) is an optical technique allowing visualisation of abnormal nuclei that may be undertaken on archival tissue. Our aim was to determine the accuracy of ICDA vs FC, and evaluate DNA ploidy as a prognostic biomarker after histologically successful treatment with photodynamic therapy (PDT).Methods:Nuclei were extracted from 40 μm sections of paraffin-embedded biopsies and processed for ICDA at UCL and FC at UW using standardised protocols. Subsequently, DNA ploidy was evaluated by ICDA on a cohort of 30 patients clear of dysplasia 1 year after aminolaevulinic acid PDT for high-grade dysplasia (HGD). The results were correlated with long-term outcome.Results:In the comparative study, 93% (41 out of 44) of cases were classified identically. Errors occurred in the near-diploid region by ICDA and the tetraploid region by FC. In the cohort study, there were 13 cases of late relapse (7 cancer, 6 HGD) and 17 patients who remained free of dysplasia after a mean follow-up of 44 months. Aneuploidy post-PDT was highly predictive for recurrent HGD or cancer with a hazard ratio of 8.2 (1.8–37.8) (log-rank P=0.001).Conclusions:ICDA is accurate for the detection of DNA ploidy abnormalities when compared with FC. After histologically successful PDT, patients with residual aneuploidy are significantly more likely to develop HGD or cancer than those who become diploid. DNA ploidy by ICDA is a valuable prognostic biomarker after ablative therapy.

Photodynamic therapy outcome for oral dysplasia

Photodynamic therapy (PDT) is a minimally invasive surgical intervention used in the management of tissue disorders. It can be applied before, or after, any of the conventional modalities, without compromising these treatments or being compromised itself.

Photodynamic therapy outcome for T1/T2 N0 oral squamous cell carcinoma

This new prospective clinical study assessed the oncological outcomes following surface illumination mTHPC‐photodynamic therapy of T1/T2 N0 oral squamous cell carcinoma (OSCC) patients.

Broadband miniature optical ultrasound probe for high resolution vascular tissue imaging.

An all-optical ultrasound probe for vascular tissue imaging was developed. Ultrasound was generated by pulsed laser illumination of a functionalized carbon nanotube composite coating on the end face of an optical fiber. Ultrasound was detected with a Fabry-Pérot (FP) cavity on the end face of an adjacent optical fiber. The probe diameter was < 0.84 mm and had an ultrasound bandwidth of ~20 MHz. The probe was translated across the tissue sample to create a virtual linear array of ultrasound transmit/receive elements. At a depth of 3.5 mm, the axial resolution was 64 µm and the lateral resolution was 88 µm, as measured with a carbon fiber target. Vascular tissues from swine were imaged ex vivo and good correspondence to histology was observed.

Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial

BACKGROUND Photochemical internalisation, a novel minimally invasive treatment, has shown promising preclinical results in enhancing and site-directing the effect of anticancer drugs by illumination, which initiates localised chemotherapy release. We assessed the safety and tolerability of a newly developed photosensitiser, disulfonated tetraphenyl chlorin (TPCS2a), in mediating photochemical internalisation of bleomycin in patients with advanced and recurrent solid malignancies. METHODS In this phase 1, dose-escalation, first-in-man trial, we recruited patients (aged ≥18 to <85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies who were clinically assessed as eligible for bleomycin chemotherapy from a single centre in the UK. Patients were given TPCS2a on day 0 by slow intravenous injection, followed by a fixed dose of 15 000 IU/m(2) bleomycin by intravenous infusion on day 4. After 3 h, the surface of the target tumour was illuminated with 652 nm laser light (fixed at 60 J/cm(2)). The TPCS2a starting dose was 0·25 mg/kg and was then escalated in successive dose cohorts of three patients (0·5, 1·0, and 1·5 mg/kg). The primary endpoints were safety and tolerability of TPCS2a; other co-primary endpoints were dose-limiting toxicity and maximum tolerated dose. The primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00993512, and has been completed. FINDINGS Between Oct 3, 2009, and Jan 14, 2014, we recruited 22 patients into the trial. 12 patients completed the 3-month follow-up period. Adverse events related to photochemical internalisation were either local, resulting from the local inflammatory process, or systemic, mostly as a result of the skin-photosensitising effect of TPCS2a. The most common grade 3 or worse adverse events were unexpected higher transient pain response (grade 3) localised to the treatment site recorded in nine patients, and respiratory failure (grade 4) noted in two patients. One dose-limiting toxicity was reported in the 1·0 mg/kg cohort (skin photosensitivity [grade 2]). Dose-limiting toxicities were reported in two of three patients at a TPCS2a dose of 1·5 mg/kg (skin photosensitivity [grade 3] and wound infection [grade 3]); thus, the maximum tolerated dose of TPCS2a was 1·0 mg/kg. Administration of TPCS2a was found to be safe and tolerable by all patients. No deaths related to photochemical internalisation treatment occurred. INTERPRETATION TPCS2a-mediated photochemical internalisation of bleomycin is safe and tolerable. We identified TPCS2a 0·25 mg/kg as the recommended treatment dose for future trials. FUNDING PCI Biotech.

Device for measuring the forces exerted on the shaft of an endoscope during colonoscopy

Colonoscopy involves advancing a flexible endoscope into and along the entire length of the colon. The procedure can be painful and carries the risk of perforating the organ, yet very little is known of the forces involved. A device to measure the forces exerted on the endoscope during colonoscopy is described. The device features a handle designed on the shape of a hinged split cylinder that locks around the endoscope, gripping it tightly. The handle has two parts, an inner part that grips the endoscope, and an outer part that is gripped by the endoscopist. The two parts are jointed together by members that transmit the forces through to the endoscope. One of the members incorporates strain gauges that measure the torque applied to the endoscope, as well as the push and pull forces. The handle can easily be unlocked and moved along the endoscope as the colonoscopy proceeds. The device is used to measure the forces applied to the endoscope during 11 routine colonoscopies, and summary results are presented. These are believed to be the first accurate measurements of the forces exerted during colonoscopy.

Optical scanning for rapid intraoperative diagnosis of sentinel node metastases in breast cancer

Intraoperative diagnosis of sentinel node metastases enables an immediate decision to proceed to axillary lymph node dissection, avoiding a second operation in node‐positive women with breast cancer.