Photodynamic therapy: Inception to application in breast cancer.

Photodynamic therapy (PDT) is already being used in the treatment of many cancers. This review examines its components and the new developments in our understanding of its immunological effects as well as pre-clinical and clinical studies, which have investigated its potential use in the treatment of breast cancer

Precision-microfabricated fiber-optic probe for intravascular pressure and temperature sensing

Small form-factor sensors are widely used in minimally invasive intravascular diagnostic procedures. Manufacturing complexities associated with miniaturizing current fiber-optic probes, particularly for multi-parameter sensing, severely constrain their adoption outside of niche fields. It is especially challenging to rapidly prototype and iterate upon sensor designs to optimize performance for medical devices. In this work, a novel technique to construct a microscale extrinsic fiber-optic sensor with a confined air cavity and sub-micron geometric resolution is presented. The confined air cavity is enclosed between a 3 μm thick pressure-sensitive distal diaphragm and a proximal temperature-sensitive plano-convex microlens segment unresponsive to changes in external pressure. Simultaneous pressure and temperature measurements are possible through optical interrogation via phase-resolved low-coherence interferometry(LCI). Upon characterization in a simulated intravascular environment, we find these sensors capable of detecting pressure changes down to 0.11 mmHg (in the range of 760 to 1060 mmHg) and temperature changes of 0.036°C (in the range 34 to 50°C). By virtue of these sensitivity values suited to intravascular physiological monitoring, and the scope of design flexibility enabled by the precision-fabricated photoresist microstructure, it is envisaged that this technique will enable construction of a wide range of fiber-optic sensors for guiding minimally invasive medical procedures

Optical interferometric temperature sensors for intravascular blood flow measurements

Direct and continuous measurements of blood flow are of significant interest in many medical specialties. In cardiology, intravascular physiological measurements can be of critical importance to determine whether coronary stenting should be performed. Intravascular pressure is a physiological parameter that is frequently measured in clinical practice. An increasing body of evidence suggests that direct measurements of blood flow, as additional physiological parameters, could improve decision making. In this study, we developed a novel fibre optic intravascular flow sensor, which enabled time-of-flight measurements by upstream thermal tagging of blood. This flow sensor comprised a temperature sensitive polymer dome at the distal end of a single mode optical fibre. The dome was continuously interrogated by low coherence interferometry to measure thermally-induced length changes with nanometre-scale resolution. Flow measurements were performed by delivering heat upstream from the sensor with a separate optical fibre, and monitoring the temperature downstream at the dome with a sample rate of 50 Hz. A fabricated flow sensor was characterized and tested within a benchtop phantom, which comprised vessels with lumen diameters that ranged from 2.5 to 5 mm. Water was used as a blood mimicking fluid. For each vessel diameter, a pump provided constant volumetric flow at rates in the range of 5 to 200 ml/min. This range was chosen to represent flow rates encountered in healthy human vessels. Laser light pulses with a wavelength of 1470 nm and durations of 0.4 s were used to perform upstream thermal tagging. These pulses resulted in downstream temperature profiles that varied with the volumetric flow rate

Fiber optic photoacoustic probe with ultrasonic tracking for guiding minimally invasive procedures

In a wide range of clinical procedures, accurate placement of medical devices such as needles and catheters is critical to optimize patient outcomes. Ultrasound imaging is often used to guide minimally invasive procedures, as it can provide real-time visualization of patient anatomy and medical devices. However, this modality can provide low image contrast for soft tissues, and poor visualization of medical devices that are steeply angled with respect to the incoming ultrasound beams. Photoacoustic sensors can provide information about the spatial distributions of tissue chromophores that could be valuable for guiding minimally invasive procedures. In this study, a system for guiding minimally invasive procedures using photoacoustic sensing was developed. This system included a miniature photoacoustic probe with three optical fibers: one with a bare end for photoacoustic excitation of tissue, a second for photoacoustic excitation of an optically absorbing coating at the distal end to transmit ultrasound, and a third with a Fabry-Perot cavity at the distal end for receiving ultrasound. The position of the photoacoustic probe was determined with ultrasonic tracking, which involved transmitting pulses from a linear-array ultrasound imaging probe at the tissue surface, and receiving them with the fiber-optic ultrasound receiver in the photoacoustic probe. The axial resolution of photoacoustic sensing was better than 70 μm, and the tracking accuracy was better than 1 mm in both axial and lateral dimensions. By translating the photoacoustic probe, depth scans were obtained from different spatial positions, and two-dimensional images were reconstructed using a frequency-domain algorithm

Music-of-Light Stethoscope: A Demonstration of the Photoacoustic Effect

In this paper we present a system aimed at demonstrating the photoacoustic (PA) effect for educational purposes. PA imaging is a hybrid imaging modality that requires no contrast agent and has a great potential for spine and brain lesion characterisation, breast cancer and blood flow monitoring notably in the context of fetal surgery. It relies on combining light excitation with ultrasound reception. Our brief was to present and explain PA imaging in a public-friendly way suitable for a variety of ages and backgrounds. We developed a simple, accessible demonstration unit using readily available materials. We used a modulated light emitting diode (LED) torch and an electronic stethoscope. The output of a music player was used for light modulation and the chest piece of the stethoscope covered by a black tape was used as an absorbing target and an enclosed chamber. This demonstration unit was presented to the public at the Bloomsbury Festival On Light in October 2015. Our stall was visited by over 100 people of varying ages. Twenty families returned in-depth evaluation questionnaires, which show that our explanations of the photoacoustic effect were well understood. Their interest in biomedical engineering was increased

Photodynamic Therapy in Primary Breast Cancer

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer

Fiber-optic Ultrasound Transducers with Carbon/PDMS Composite Coatings

Novel ultrasound transducers were created with a composite of carbon nanotubes (CNTs) and polydimethylsiloxane (PDMS) that was dip coated onto the end faces of optical fibers. The CNTs were functionalized with oleylamine to allow for their dissolution in xylene, a solvent of PDMS. Ultrasound pulses were generated by illuminating the composite coating with pulsed laser light. At distances of 2 to 16 mm from the end faces, ultrasound pressures ranged from 0.81 to 0.07 MPa and from 0.27 to 0.03 MPa with 105 and 200 μm core fibers, respectively. Using an optical fiber hydrophone positioned adjacent to the coated 200 µm core optical fiber, ultrasound reflectance measurements were obtained from the outer surface of a sheep heart ventricle. The results of this study suggest that ultrasound transducers that comprise optical fibers with CNT-PDMS composite coatings may be suitable for miniature medical imaging probes

Ultrasonic Needle Tracking with Dynamic Electronic Focusing

Accurate identification of the needle tip is a key challenge with ultrasound-guided percutaneous interventions in regional anaesthesia, foetal surgery and cardiovascular medicine. In this study, we developed an ultrasonic needle tracking system in which the measured needle tip location was used to set the electronic focus of the external ultrasound imaging probe. In this system, needle tip tracking was enabled with a fibre-optic ultrasound sensor that was integrated into a needle stylet, and the A-lines recorded by the sensor were processed to generate tracking images of the needle tip. The needle tip position was estimated from the tracking images. The dependency of the tracking image on the electronic focal depth of the external ultrasound imaging probe was studied in a water bath and with needle insertions into a clinical training phantom. The variability in the estimated tracked position of the needle tip, with the needle tip at fixed depths in the imaging plane across a depth range from 0.5 to 7.5 cm, was studied. When the electronic focus was fixed, the variability of tracked position was found to increase with distance from that focus. The variability with the fixed focus was found to depend on the the relative distance between the needle tip and focal depth. It was found that with dynamic focusing, the maximum variability of tracked position was below 0.31 mm, as compared with 3.97 mm for a fixed focus

Design of sEMG assembly to detect external anal sphincter activity: a proof of concept

Objective: Conditional trans-rectal stimulation of the pudendal nerve could provide a viable solution to treat hyperreflexive bladder in spinal cord injury. A set threshold of the amplitude estimate of the external anal sphincter surface electromyography (sEMG) may be used as the trigger signal. The efficacy of such a device should be tested in a large scale clinical trial. As such a probe should remain in situ for several hours while patients attend to their daily routine, the recording electrodes should be designed to be large enough to maintain good contact while observing design constraints. The objective of this study was to arrive at a design for intra-anal sEMG recording electrodes for the subsequent clinical trials while deriving the possible recording and processing parameters. 
 Approach: Having in mind existing solutions and based on theoretical and anatomical considerations, a set of four multi-electrode probes were designed and developed. These were tested in a healthy subject and the measured sEMG traces were recorded and appropriately processed.
 Main results: It was shown that while comparatively large electrodes record sEMG traces that are not sufficiently correlated with the external anal sphincter contractions, smaller electrodes may not maintain a stable electrode tissue contact. It was shown that 3 mm wide and 1 cm long electrodes with 5 mm inter-electrode spacing, in agreement with Nyquist sampling, placed 1 cm from the orifice may intra-anally record a sEMG trace sufficiently correlated with external anal sphincter activity.
 Significance: The outcome of this study can be used in any biofeedback, treatment or diagnostic application where the activity of the external anal sphincter sEMG should be detected for an extended period of time

Elastic scattering spectroscopy for early detection of breast cancer: partially supervised Bayesian image classification of scanned sentinel lymph nodes

Sentinel lymph node biopsy is a standard diagnosis procedure to determine whether breast cancer has spread to the lymph glands in the armpit (the axillary nodes). The metastatic status of the sentinel node (the first node in the axillary chain that drains the affected breast) is the determining factor in surgery between conservative lumpectomy and more radical mastectomy including axillary node excision. The traditional assessment of the node requires sample preparation and pathologist interpretation. An automated elastic scattering spectroscopy (ESS) scanning device was constructed to take measurements from the entire cut surface of the excised sentinel node and to produce ESS images for cancer diagnosis. Here, we report on a partially supervised image classification scheme employing a Bayesian multivariate, finite mixture model with a Markov random field (MRF) spatial prior. A reduced dimensional space was applied to represent the scanning data of the node by a statistical image, in which normal, metastatic, and nonnodal-tissue pixels are identified. Our results show that our model enables rapid imaging of lymph nodes. It can be used to recognize nonnodal areas automatically at the same time as diagnosing sentinel node metastases with sensitivity and specificity of 85% and 94%, respectively. ESS images can help surgeons by providing a reliable and rapid intraoperative determination of sentinel nodal metastases in breast cancer