Jim O'Doherty

Comparison of instruments for investigation of microcirculatory blood flow and red blood cell concentration

The use of laser Doppler perfusion imaging (LDPI) and laser speckle perfusion imaging (LSPI) is well known in the noninvasive investigation of microcirculatory blood flow. This work compares the two techniques with the recently developed tissue viability (TiVi) imaging system, which is proposed as a useful tool to quantify red blood cell concentration in microcirculation. Three systems are evaluated with common skin tests such as the use of vasodilating and vasoconstricting drugs (methlynicotinate and clobetasol, respectively) and a reactive hyperaemia maneuver (using a sphygmomanometer). The devices investigated are the laser Doppler line scanner (LDLS), the laser speckle perfusion imager (FLPI)-both from Moor Instruments (Axminster, United Kingdom)-and the TiVi imaging system (WheelsBridge AB, Linkoping, Sweden). Both imaging and point scanning by the devices are used to quantify the provoked reactions. Perfusion images of vasodilatation and vasoconstriction are acquired with both LDLS and FLPI, while TiVi images are acquired with the TiVi imager. Time acquisitions of an averaged region of interest are acquired for temporal studies such as the reactive hyperaemia. In contrast to the change in perfusion over time with pressure, the TiVi imager shows a different response due its measurement of blood concentration rather than perfusion. The responses can be explained by physiological understanding. Although the three devices sample different compartments of tissue, and output essentially different variables, comparisons can be seen between the three systems. The LDLS system proves to be suited to measurement of perfusion in deeper vessels, while FLPI and TiVi showed sensitivity to more superficial nutritional supply. LDLS and FLPI are insensitive to the action of the vasoconstrictor, while TiVi shows the clear boundaries of the reaction. Assessment of the resolution, penetration depth, and acquisition rate of each instrument show complimentary features that should be taken into account when choosing a system for a particular clinical measurement.

Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation.

Background/aims: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non‐invasive, more user‐independent and objective methods are available today. Limited portability, high cost, lack of robustness and non‐specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy‐to‐use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology.

Tissue viability (TiVi) imaging: temporal effects of local occlusion studies in the volar forearm

Tissue Viability (TiVi) imaging is a promising new technology for the assessment of microcirculation in the upper human dermis. Although the technique is easily implemented and develops large amounts of observational data, its role in the clinical workplace awaits the development of standardised protocols required for routine clinical practice. The present study investigates the use of TiVi technology in a human, in vivo, localized, skin blood flow occlusion protocol. In this feasibility study, the response of the cutaneous microcirculation after provocation on the volar surface of the forearm was evaluated using a high temporal-low spatial resolution TiVi camera. 19 healthy subjects - 10 female and 9 male - were studied after a localized pressure was applied for 5 different time periods ranging from 5 to 25 seconds. Areas corresponding to 100 x 100 pixels (2.89 cm(2)) were monitored for 60 seconds prior to, during and after each occlusion period. Our results demonstrated the removal of blood from the local area and a hyperaemic response supporting the suitability of TiVi imaging for the generation of detailed provocation response data of relevance for the physiological function of the skin microcirculation in health and disease.

The importance of scatter correction for the assessment of lung shunting prior to yttrium-90 radioembolization therapy.

BackgroundTreatment of inoperable hepatocellular carcinoma or secondary metastases by radioembolization using yttrium-90 (90Y) microspheres is a promising method for the treatment of unresectable liver metastases. A pretreatment scintigraphy planar scan using 99mTc-labelled macroaggregated albumin (99mTc-MAA) injected directly into the hepatic artery is carried out to assess the degree of portal shunting of blood between the liver and the lungs. The quantitative results of this scan are used to modulate the activity of therapeutic 90Y microspheres injected into the patient to limit the radiation dose received by the lungs. The presence of scattered events in the MAA lung shunt scan leads to an overestimation of the true shunting ratio, which in turn leads to the administered therapeutic activity being lowered unnecessarily to comply with the protocols of radiation protection. Overall, this may impact the efficacy of treatment. Materials and methodsThis study analyses the impact of a window-based analytical scatter-correction method on lung shunt analysis using an anthropomorphic torso phantom, and retrospectively analysed three patient case studies. ResultsOur results of scatter in the phantom show a marked decrease in the lung shunt percentage. Clinical analysis of patient data shows that the lung shunt percentage can be overestimated by up to 50% in clinical cases, and depending on the lung shunt percentage, the efficacy of treatment by therapeutic dose reduction may be compromised. ConclusionOur results indicate that scatter correction should be used on 90Y pretreatment 99mTc-MAA scans in order to more accurately assess the lung shunting percentage before therapy.

Multimodal Partial Volume Correction – Application to 18F-Fluoride PET/CT bone metastases studies

18F-fluoride PET/CT offers the opportunity for accurate skeletal metastasis staging, compared with conventional imaging methods. 18F-fluoride is a bone-specific tracer whose uptake depends on osteoblastic activity. Because of the resulting increase in bone mineralization and sclerosis, the osteoblastic process can also be detected morphologically in CT images. Although CT is characterized by high resolution, the potential of PET is limited by its lower spatial resolution and the resulting partial-volume effect. In this context, the synergy between PET and CT presents an opportunity to resolve this limitation using a novel multimodal approach called synergistic functional–structural resolution recovery (SFS-RR). Its performance is benchmarked against current resolution recovery technology using the point-spread function (PSF) of the scanner in the reconstruction procedure. Methods: The SFS-RR technique takes advantage of the multiresolution property of the wavelet transform applied to both functional and structural images to create a high-resolution PET image that exploits the structural information of CT. Although the method was originally conceived for PET/MR imaging of brain data, an ad hoc version for whole-body PET/CT is proposed here. Three phantom experiments and 2 datasets of metastatic bone 18F-fluoride PET/CT images from primary prostate and breast cancer were used to test the algorithm performances. The SFS-RR images were compared with the manufacturer’s PSF-based reconstruction using the standardized uptake value (SUV) and the metabolic volume as metrics for quantification. Results: When compared with standard PET images, the phantom experiments showed a bias reduction of 14% in activity and 1.3 cm3 in volume estimates for PSF images and up to 20% and 2.5 cm3 for the SFS-RR images. The SFS-RR images were characterized by a higher recovery coefficient (up to 60%) whereas noise levels remained comparable to those of standard PET. The clinical data showed an increase in the SUV estimates for SFS-RR images up to 34% for peak SUV and 50% for maximum SUV and mean SUV. Images were also characterized by sharper lesion contours and better lesion detectability. Conclusion: The proposed methodology generates PET images with improved quantitative and qualitative properties. Compared with standard methods, SFS-RR provides superior lesion segmentation and quantification, which may result in more accurate tumor characterization.

Automated x-ray/light field congruence using the LINAC EPID panel.

PURPOSE X-ray/light field alignment is a test described in many guidelines for the routine quality control of clinical linear accelerators (LINAC). Currently, the gold standard method for measuring alignment is through utilization of radiographic film. However, many modern LINACs are equipped with an electronic portal imaging device (EPID) that may be used to perform this test and thus subsequently reducing overall cost, processing, and analysis time, removing operator dependency and the requirement to sustain the departmental film processor. METHODS This work describes a novel method of utilizing the EPID together with a custom inhouse designed jig and automatic image processing software allowing measurement of the light field size, x-ray field size, and congruence between them. The authors present results of testing the method for aS1000 and aS500 Varian EPID detectors for six LINACs at a range of energies (6, 10, and 15 MV) in comparison with the results obtained from the use of radiographic film. RESULTS Reproducibility of the software in fully automatic operation under a range of operating conditions for a single image showed a congruence of 0.01 cm with a coefficient of variation of 0. Slight variation in congruence repeatability was noted through semiautomatic processing by four independent operators due to manual marking of positions on the jig. Testing of the methodology using the automatic method shows a high precision of 0.02 mm compared to a maximum of 0.06 mm determined by film processing. Intraindividual examination of operator measurements of congruence was shown to vary as much as 0.75 mm. Similar congruence measurements of 0.02 mm were also determined for a lower resolution EPID (aS500 model), after rescaling of the image to the aS1000 image size. CONCLUSIONS The designed methodology was proven to be time efficient, cost effective, and at least as accurate as using the gold standard radiographic film. Additionally, congruence testing can be easily performed for all four cardinal gantry angles which can be difficult when using radiographic film. Therefore, the authors propose it can be used as an alternative to the radiographic film method allowing decommissioning of the film processor.

Real time diffuse reflectance polarisation spectroscopy imaging to evaluate skin microcirculation

This article describes the theoretical development and design of a real-time microcirculation imaging system, an extension from a previously technology developed by our group. The technology utilises polarisation spectroscopy, a technique used in order to selectively gate photons returning from various compartments of human skin tissue, namely from the superficial layers of the epidermis, and the deeper backscattered light from the dermal matrix. A consumer-end digital camcorder captures colour data with three individual CCDs, and a custom designed light source consisting of a 24 LED ring light provides broadband illumination over the 400 nm - 700 nm wavelength region. Theory developed leads to an image processing algorithm, the output of which scales linearly with increasing red blood cell (RBC) concentration. Processed images are displayed online in real-time at a rate of 25 frames s-1, at a frame size of 256 x 256 pixels, and is limited only by computer RAM memory and processing speed. General demonstrations of the technique in vivo display several advantages over similar technology.

Dynamic microvascular responses with a high speed TiVi imaging system

TiVi technology presents a high resolution, low speed methodology for imaging microcirculation. Recently, the TiVi system was adapted to produce a high speed system capable of analysing dynamic responses from human tissues at a frame rate of 30 frames per second. We present results based on this system by investigating dynamic responses such as arterial pulsations both from a controlled flow model and in vivo tissue sites. We also quantify the effects of sympathetic vasomotion, a biological effect which is evident in many tissue sites, and show that the effects of arterial pulsations and vasomotion on the resulting TiVi time traces are easily determined.

Three dosimetry models of lipoma arborescens treated by 90Y synovectomy.

PURPOSE Lipoma arborescens (LA) is a benign intra-articular lipomatous proliferation of the synovial membrane. This extremely rare condition has previously been treated by intra-articular (90)Y radiosynoviorthesis but dosimetry literature on this form of radionuclide therapy is nonexistent. The authors detail methodology for successful treatment of LA and provide for the first time estimates of radiation dosimetry. The authors also analyze the biodistribution of the radiopharmaceutical over the course of the patients treatment through sequential imaging. METHODS A patient with bilateral LA underwent intracavity injection of (90)Y citrate colloid to the right and left knee joint spaces (181 and 198 MBq, respectively). SPECT/CT datasets were acquired over 9 days to quantify the biodistribution and kinetics of the radiopharmaceutical. Radiation dosimetry was performed using the MIRD schema (through OLINDA software), a custom voxel-based method, and a direct Monte Carlo calculation (OEDIPE). RESULTS Follow-up MRI showed marked reduction in LA size in both knees. Mean absorbed doses to the LA were 21.2 ± 0.8 and 42.9 ± 2.3 Gy using OLINDA, 8.1 ± 0.3 and 16.7 ± 0.5 Gy using voxel based methodology, and 8.2 ± 0.3 and 15.7 ± 0.5 Gy for OEDIPE in the right and left LA, respectively. Distribution of the radiopharmaceutical within the joint space alters over the imaging period, with less than 1% of the remaining activity having moved posteriorly in the knee cavity. No uptake was detected outside of the joint space after assessment with whole-body scintigraphy. CONCLUSIONS An activity of approximately 185 MBq successfully relieved clinical symptoms of LA. There was good correlation between direct Monte Carlo and voxel based techniques, but OLINDA was shown to overestimate the absorbed dose to the tumor. Accurate dosimetry may help select an activity more tailored to the specific size and location of the LA.

Lipoma Arborescens Successfully Treated With 90Y Synovectomy

Lipoma arborescens (LA) in the knee is a benign intra-articular lipomatous proliferation of the synovial membrane, and data on treatment of LA by radionuclide therapy is sparse. We present a rare case of bilateral LA in the knees successfully treated with injection of Y-citrate colloid. We assessed the biodistribution of the radiopharmaceutical through the use of SPECT/CT imaging. Our images show slight redistribution of the radiocolloid in the knee joint, whereas most of the radioactivity remains localized around the LA. MRI scans confirmed the efficacy of this treatment, with a significant reduction in LA volume after 6 months.