Table of contents

In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues. This review emphasizes the newer techniques of SOCT and molecular imaging OCT, which show excellent potential for clinical application but have yet to be well reviewed in the literature. SOCT elucidates tissue characteristics, such as oxygenation and carcinogenesis, by detecting wavelength-dependent absorption and scattering of light in tissues. While SOCT measures endogenous biochemical distributions, molecular imaging OCT detects exogenous molecular contrast agents. These newer advances in functional OCT broaden the potential clinical application of OCT by providing novel ways to understand tissue activity that cannot be accomplished by other current imaging methodologies.

Cyclotron production of ^99mTc through the ¹⁰⁰Mo(p,2n) ^99mTc reaction channel is actively being investigated as an alternative to reactor-based ⁹⁹Mo generation by nuclear fission of ²³⁵U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional ^99mTc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity ^99mTc. However, variations in proton beam currents and the thickness and isotopic composition of enriched ¹⁰⁰Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute ^99mTc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including ¹⁰⁰Mo target thicknesses and proton beam currents, and reproducibility of absolute ^99mTc yields (defined as the end of bombardment (EOB) ^99mTc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB ^99mTc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in ^99mTc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of ^99mTc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced ^99mTc.

Liver vessel segmentation in CTA images is a challenging task, especially in the case of noisy images. This paper investigates whether pre-filtering improves liver vessel segmentation in 3D CTA images. We introduce a quantitative evaluation of several well-known filters based on a proposed liver vessel segmentation method on CTA images. We compare the effect of different diffusion techniques i.e. Regularized Perona–Malik, Hybrid Diffusion with Continuous Switch and Vessel Enhancing Diffusion as well as the vesselness approaches proposed by Sato, Frangi and Erdt. Liver vessel segmentation of the pre-processed images is performed using a histogram-based region grown with local maxima as seed points. Quantitative measurements (sensitivity, specificity and accuracy) are determined based on manual landmarks inside and outside the vessels, followed by T-tests for statistic comparisons on 51 clinical CTA images. The evaluation demonstrates that all the filters make liver vessel segmentation have a significantly higher accuracy than without using a filter (p  <  0.05); Hybrid Diffusion with Continuous Switch achieves the best performance. Compared to the diffusion filters, vesselness filters have a greater sensitivity but less specificity. In addition, the proposed liver vessel segmentation method with pre-filtering is shown to perform robustly on a clinical dataset having a low contrast-to-noise of up to 3 (dB). The results indicate that the pre-filtering step significantly improves liver vessel segmentation on 3D CTA images.

In the past decade, several different radiotherapy treatment plan evaluation and optimization schemes have been proposed as viable approaches, aiming for dose escalation or an increase of healthy tissue sparing. In particular, it has been argued that dose-mass plan evaluation and treatment plan optimization might be viable alternatives to the standard of care, which is realized through dose-volume evaluation and optimization. The purpose of this investigation is to apply dose-mass optimization to a cohort of lung cancer patients and compare the achievable healthy tissue sparing to that one achievable through dose-volume optimization.

Fourteen non-small cell lung cancer (NSCLC) patient plans were studied retrospectively. The range of tumor motion was less than 0.5 cm and motion management in the treatment planning process was not considered. For each case, dose-volume (DV)-based and dose-mass (DM)-based optimization was performed. Nine-field step-and-shoot IMRT was used, with all of the optimization parameters kept the same between DV and DM optimizations. Commonly used dosimetric indices (DIs) such as dose to 1% the spinal cord volume, dose to 50% of the esophageal volume, and doses to 20 and 30% of healthy lung volumes were used for cross-comparison. Similarly, mass-based indices (MIs), such as doses to 20 and 30% of healthy lung masses, 1% of spinal cord mass, and 33% of heart mass, were also tallied. Statistical equivalence tests were performed to quantify the findings for the entire patient cohort.

Both DV and DM plans for each case were normalized such that 95% of the planning target volume received the prescribed dose. DM optimization resulted in more organs at risk (OAR) sparing than DV optimization. The average sparing of cord, heart, and esophagus was 23, 4, and 6%, respectively. For the majority of the DIs, DM optimization resulted in lower lung doses. On average, the doses to 20 and 30% of healthy lung were lower by approximately 3 and 4%, whereas lung volumes receiving 2000 and 3000 cGy were lower by 3 and 2%, respectively. The behavior of MIs was very similar. The statistical analyses of the results again indicated better healthy anatomical structure sparing with DM optimization.

The presented findings indicate that dose-mass–based optimization results in statistically significant OAR sparing as compared to dose-volume–based optimization for NSCLC. However, the sparing is case-dependent and it is not observed for all tallied dosimetric endpoints.

This paper introduces a hybrid method for performing detection studies in projection image based modalities, based on image acquisitions of target objects and patients. The method was used to compare 2D mammography and digital breast tomosynthesis (DBT) in terms of the detection performance of spherical densities and microcalcifications. The method starts with the acquisition of spheres of different glandular equivalent densities and microcalcifications of different sizes immersed in a homogeneous breast tissue simulating medium. These target objects are then segmented and the subsequent templates are fused in projection images of patients and processed or reconstructed. This results in hybrid images with true mammographic anatomy and clinically relevant target objects, ready for use in observer studies. The detection study of spherical densities used 108 normal and 178 hybrid 2D and DBT images; 156 normal and 321 hybrid images were used for the microcalcifications. Seven observers scored the presence/absence of the spheres/microcalcifications in a square region via a 5-point confidence rating scale. Detection performance in 2D and DBT was compared via ROC analysis with sub-analyses for the density of the spheres, microcalcification size, breast thickness and z-position. The study was performed on a Siemens Inspiration tomosynthesis system using patient acquisitions with an average age of 58 years and an average breast thickness of 53 mm providing mean glandular doses of 1.06 mGy (2D) and 2.39 mGy (DBT). Study results showed that breast tomosynthesis (AUC = 0.973) outperformed 2D (AUC = 0.831) for the detection of spheres (p  <  0.0001) and this applied for all spherical densities and breast thicknesses. By way of contrast, DBT was worse than 2D for microcalcification detection (AUC_2D = 0.974, AUC_DBT = 0.838, p  <  0.0001), with significant differences found for all sizes (150–354 µm), for breast thicknesses above 40 mm and for heights above the detector of 20 mm and above. In conclusion, the hybrid method was successfully used to produce images for a detection study; results showed breast tomosynthesis outperformed 2D for spherical densities while further optimization of DBT for microcalcifications is suggested.

The measurement of output factors (OF) for the small photon beams generated by Leksell Gamma Knife® (LGK) radiotherapy units is a challenge for the physicist due to the under or over estimation of these factors by a vast majority of the detectors commercially available. Output correction factors, introduced in the international formalism published by Alfonso (2008 Med. Phys.35 5179–86), standardize the determination of OFs for small photon beams by correcting detector-reading ratios to yield OFs in terms of absorbed-dose ratios. In this work output correction factors for a number of detectors have been determined for LGK Perfexion™ ⁶⁰Co γ-ray beams by Monte Carlo (MC) calculations and measurements. The calculations were made with the MC system PENELOPE, scoring the energy deposited in the active volume of the detectors and in a small volume of water; the detectors simulated were two silicon diodes, one liquid ionization chamber (LIC), alanine and TLD. The calculated LIC output correction factors were within ± 0.4%, and this was selected as the reference detector for experimental determinations where output correction factors for twelve detectors were measured, normalizing their readings to those of the LIC. The MC-calculated and measured output correction factors for silicon diodes yielded corrections of up to 5% for the smallest LGK collimator size of 4 mm diameter. The air ionization chamber measurements led to extremely large output correction factors, caused by the well-known effect of partial volume averaging. The corrections were up to 7% for the natural diamond detector in the 4 mm collimator, also due to partial volume averaging, and decreased to within about ± 0.6% for the smaller synthetic diamond detector. The LIC, showing the smallest corrections, was used to investigate machine-to-machine output factor differences by performing measurements in four LGK units with different dose rates. These resulted in OFs within ± 0.6% and ± 0.2% for the 4 mm and 8 mm collimators, respectively, providing evidence for the use of generic OFs for these LGK beams. Using the experimentally derived output correction factors, OFs can be measured using a wide range of commercially available detectors.

As the skull induces strong aberrations in phase and amplitude during transcranial treatment of brain surgery, high-intensity focused ultrasound suffers degradation in beam shape and deposits significant heat in the skull which may cause thermal damage to the bone and surrounding tissue. The goal of this study is to optimize the transcranial pressure and thermal fields to reduce thermal damage to the skull and simultaneously concentrate more energy in the focal region and make its size controllable during transcranial brain tumor treatment by modulating the excitation signals of the transducer array (including the phase and amplitude) and superposing the signals used to reduce peak pressure in the skull. A 3D numerical model was developed based on the reconstructed images from high-resolution CT scans of a human skull and a 64-element phased array to simulate acoustic propagation and thermal behavior calculated by the finite-difference time domain method. The simulation showed that more energy was focused at the setting target with little temperature elevation in the skull after correcting phase and amplitude and reducing peak pressure in the skull; through modulating the input intensity of arrays, the volume of focal regions located off-axis could be made equal to the volume achieved with on-axis focusing.

Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment planning utilized a combination of a commercial treatment planning system and an in-house risk-optimization algorithm. When normal-tissue dose constraints were incorporated in treatment planning, the risk model that incorporated the effects of fractionation, initiation, inactivation, repopulation and promotion selected a combination of anterior and lateral beams, which lowered the relative risk by 21% for the bladder and 30% for the rectum compared to the lateral-opposed beam arrangement. Other results were found for other risk models.

A segmental two-parameter empirical deformable model is proposed for evaluating regional motion abnormality of the left ventricle. Short-axis tagged MRI scans were acquired from 10 healthy subjects and 10 postinfarct patients. Two motion parameters, contraction and rotation, were quantified for each cardiac segment by fitting the proposed model using a non-rigid registration algorithm. The accuracy in motion estimation was compared to a global model approach. Motion parameters extracted from patients were correlated to infarct transmurality assessed with delayed-contrast-enhanced MRI. The proposed segmental model allows markedly improved accuracy in regional motion analysis as compared to the global model for both subject groups (1.22–1.40 mm versus 2.31–2.55 mm error). By end-systole, all healthy segments experienced radial displacement by ~25–35% of the epicardial radius, whereas the 3 short-axis planes rotated differently (basal: 3.3°; mid:  −1° and apical:  −4.6°) to create a twisting motion. While systolic contraction showed clear correspondence to infarct transmurality, rotation was nonspecific to either infarct location or transmurality but could indicate the presence of functional abnormality. Regional contraction and rotation derived using this model could potentially aid in the assessment of severity of regional dysfunction of infarcted myocardium.

In magnetic particle imaging (MPI), the relation between the particle distribution and the measurement signal can be described by a linear system of equations. For 1D imaging, it can be shown that the system matrix can be expressed as a product of a convolution matrix and a Chebyshev transformation matrix. For multidimensional imaging, the structure of the MPI system matrix is not yet fully explored as the sampling trajectory complicates the physical model. It has been experimentally found that the MPI system matrix rows have symmetries and look similar to the tensor products of Chebyshev polynomials. In this work we will mathematically prove that the 2D MPI system matrix has symmetries that can be used for matrix compression.

A full-field speckle interferometry method for non-contact and prospectively high speed Photoacoustic Tomography is introduced and evaluated as proof of concept. Thermoelastic pressure induced changes of the objects topography are acquired in a repetitive mode without any physical contact to the object. In order to obtain high acquisition speed, the object surface is illuminated by laser pulses and imaged onto a high speed camera chip. In a repetitive triple pulse mode, surface displacements can be acquired with nanometre sensitivity and an adjustable sampling rate of e.g. 20 MHz with a total acquisition time far below one second using kHz repetition rate lasers. Due to recurring interferometric referencing, the method is insensitive to thermal drift of the object due to previous pulses or other motion. The size of the investigated area and the spatial and temporal resolution of the detection are scalable. In this study, the approach is validated by measuring a silicone phantom and a porcine skin phantom with embedded silicone absorbers. The reconstruction of the absorbers is presented in 2D and 3D. The sensitivity of the measurement with respect to the photoacoustic detection is discussed. Potentially, Photoacoustic Imaging can be brought a step closer towards non-anaesthetized in vivo imaging and new medical applications not allowing acoustic contact, such as neurosurgical monitoring or burnt skin investigation.

The treatment of superficial skin lesions via daylight activated photodynamic therapy (PDT) has been explored theoretically with three dimensional (3D) Monte Carlo radiation transfer simulations. For similar parameters and conditions, daylight activated PDT was compared to conventional PDT using a commercially available light source. Under reasonable assumptions for the optical properties of the tissue, protoporphyrin IX (PpIX) concentration and a treatment dose of 75 J cm⁻², it was found that during a clear summer day an effective treatment depth of over 2 mm can be achieved after 30 min of daylight illumination at a latitude of 56 degrees North. The same light dose would require 2.5 h of daylight illumination during an overcast summer day where a treatment depth of about 2 mm can be achieved. For conventional PDT the developed model suggests that 15 min of illumination is required to deliver a light dose of 75 J cm⁻², which would result in an effective treatment depth of about 3 mm. The model developed here allows for the determination of photo-toxicity in skin tissue as a function of depth for different weather conditions as well as for conventional light sources. Our theoretical investigation supports clinical studies and shows that daylight activated PDT has the potential for treating superficial skin lesions during different weather conditions.

Correction of an inhomogeneous magnetic field is proposed using partial differential phases in magnetic resonance imaging. Estimation of the inhomogeneous magnetic field from a measured phase is not an easy task due to phase wrapping and chemical-dependent phase shifts. Using the proposed partial differential phase technique, such problems are resolved. The proposed technique uses most of the 3D pixel data regardless of chemical compounds for the estimation of the inhomogeneous magnetic field. A large number of partial difference data compared to the number of expansion terms for the model of inhomogeneous magnetic field provides a very stable estimation, robust to noise. The technique is applicable to in vivo shimming, water-fat imaging, eddy current compensation, and most phase-related measurements and imaging. The efficacy of the proposed technique is demonstrated with in vivo water-fat imaging.

The purpose of this study was to find the most accurate model for radiochromic film dosimetry by comparing different channel independent perturbation models. A model selection approach based on (algorithmic) information theory was followed, and the results were validated using gamma-index analysis on a set of benchmark test cases. Several questions were addressed: (a) whether incorporating the information of the non-irradiated film, by scanning prior to irradiation, improves the results; (b) whether lateral corrections are necessary when using multichannel models; (c) whether multichannel dosimetry produces better results than single-channel dosimetry; (d) which multichannel perturbation model provides more accurate film doses. It was found that scanning prior to irradiation and applying lateral corrections improved the accuracy of the results. For some perturbation models, increasing the number of color channels did not result in more accurate film doses. Employing Truncated Normal perturbations was found to provide better results than using Micke–Mayer perturbation models. Among the models being compared, the triple-channel model with Truncated Normal perturbations, net optical density as the response and subject to the application of lateral corrections was found to be the most accurate model. The scope of this study was circumscribed by the limits under which the models were tested. In this study, the films were irradiated with megavoltage radiotherapy beams, with doses from about 20–600 cGy, entire (8 inch  × 10 inch) films were scanned, the functional form of the sensitometric curves was a polynomial and the different lots were calibrated using the plane-based method.

Carbon-ion radiotherapy treatment plans are designed on the assumption that the beams are delivered instantaneously, irrespective of actual dose-delivery time structure in a treatment session. As the beam lines are fixed in the vertical and horizontal directions at our facility, beam delivery is interrupted in multi-field treatment due to the necessity of patient repositioning within the fields. Single-fractionated treatment for non-small cell lung cancer (NSCLC) is such a case, in which four treatment fields in multiple directions are delivered in one session with patient repositioning during the session. The purpose of this study was to investigate the effects of the period of dose delivery, including interruptions due to patient repositioning, on tumor control probability (TCP) of NSCLC. All clinical doses were weighted by relative biological effectiveness (RBE) evaluated for instantaneous irradiation. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions induced in DNA were applied to the single-fractionated treatment of NSCLC. Treatment plans were made for an NSCLC case for various prescribed doses ranging from 25 to 50 Gy (RBE), on the assumption of instantaneous beam delivery. These plans were recalculated by varying the interruption time τ ranging from 0 to 120 min between the second and third fields for continuous irradiations of 3 min per field based on the MKM. The curative doses that would result in a TCP of 90% were deduced for the respective interruption times. The curative dose was 34.5 Gy (RBE) for instantaneous irradiation and 36.6 Gy (RBE), 39.2 Gy (RBE), 41.2 Gy (RBE), 43.3 Gy (RBE) and 44.4 Gy (RBE) for τ = 0 min, 15 min, 30 min, 60 min and 120 min, respectively. The realistic biological effectiveness of therapeutic carbon-ion beam decreased with increasing interruption time. These data suggest that the curative dose can increase by 20% or more compared to the planned dose if the interruption time extends to 30 min or longer. These effects should be considered in carbon-ion radiotherapy treatment planning if a longer dose-delivery procedure time is anticipated.

Phase contrast mammography using a grating interferometer is an emerging technology for breast imaging. It provides complementary information to the conventional absorption-based methods. Additional diagnostic values could be further obtained by retrieving quantitative information from the three physical signals (absorption, differential phase and small-angle scattering) yielded simultaneously. We report a non-parametric quantitative volumetric breast density estimation method by exploiting the ratio (dubbed the R value) of the absorption signal to the small-angle scattering signal. The R value is used to determine breast composition and the volumetric breast density (VBD) of the whole breast is obtained analytically by deducing the relationship between the R value and the pixel-wise breast density. The proposed method is tested by a phantom study and a group of 27 mastectomy samples. In the clinical evaluation, the estimated VBD values from both cranio–caudal (CC) and anterior–posterior (AP) views are compared with the ACR scores given by radiologists to the pre-surgical mammograms. The results show that the estimated VBD results using the proposed method are consistent with the pre-surgical ACR scores, indicating the effectiveness of this method in breast density estimation. A positive correlation is found between the estimated VBD and the diagnostic ACR score for both the CC view ($p=0.033$) and AP view ($p=0.001$). A linear regression between the results of the CC view and AP view showed a correlation coefficient γ = 0.77, which indicates the robustness of the proposed method and the quantitative character of the additional information obtained with our approach.

Optimization methods are critical to radiation therapy. A new technology, quantum annealing (QA), employs novel hardware and software techniques to address various discrete optimization problems in many fields. We report on the first application of quantum annealing to the process of beamlet intensity optimization for IMRT.

We apply recently-developed hardware which natively exploits quantum mechanical effects for improved optimization. The new algorithm, called QA, is most similar to simulated annealing, but relies on natural processes to directly minimize a system's free energy. A simple quantum system is slowly evolved into a classical system representing the objective function. If the evolution is sufficiently slow, there are probabilistic guarantees that a global minimum will be located.

To apply QA to IMRT-type optimization, two prostate cases were considered. A reduced number of beamlets were employed, due to the current QA hardware limitations. The beamlet dose matrices were computed using CERR and an objective function was defined based on typical clinical constraints, including dose-volume objectives, which result in a complex non-convex search space. The objective function was discretized and the QA method was compared to two standard optimization methods, simulated annealing and Tabu search, run on a conventional computing cluster.

Based on several runs, the average final objective function value achieved by the QA was 16.9 for the first patient, compared with 10.0 for Tabu and 6.7 for the simulated annealing (SA) method. For the second patient, the values were 70.7 for the QA, 120.0 for Tabu and 22.9 for the SA. The QA algorithm required 27–38% of the time required by the other two methods.

In this first application of hardware-enabled QA to IMRT optimization, its performance is comparable to Tabu search, but less effective than the SA in terms of final objective function values. However, its speed was 3–4 times faster than the other two methods. This initial experiment suggests that more research into QA-based heuristics may offer significant speedup over conventional clinical optimization methods, as quantum annealing hardware scales to larger sizes.

Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation therapy using photon beams. Recently, experimental studies have been carried out using proton beams showing the GNP enhanced responses in proton therapy. In this work, we established a biological model to investigate the change in survival of irradiated cells due to the radiosensitizing effect of gold nanoparticles. Results for proton, megavoltage (MV) photon and kilovoltage (kV) photon beams are compared. For each particle source, we assessed various treatment depths, GNP cellular uptakes and sizes. We showed that kilovoltage photons caused the highest enhancement due to the high interaction probability between GNPs and kV photons. The cell survival fraction can be significantly reduced for both proton and MV photon irradiations if GNPs accumulate in the cell. For instance, the sensitizer enhancement ratio (SER) is 1.33 for protons in the middle of a spread out Bragg peak for 1 µM of internalized 50 nm GNPs. If the GNPs can all be internalized into the cell nucleus, the SER for proton therapy increases from 1.33 to 1.81. The results also show that for the same mass of GNPs in the cells, one can expect the greatest sensitization by smaller GNPs, i.e. a SER of 1.33 for 1 µM of internalized 50 nm GNPs and a SER of 3.98 for the same mass of 2 nm GNPs. We concluded that if the GNPs cannot be internalized into the cytoplasm, no GNP enhancement will be observed for proton treatment. Meanwhile, proton radiotherapy can potentially be enhanced with GNPs if they can be internalized into cells, and especially the cell nucleus.

Statistical event reconstruction techniques can give better results for gamma cameras than the traditional centroid method. However, implementation of such techniques requires detailed knowledge of the photomultiplier tube light-response functions. Here we describe an iterative method which allows one to obtain the response functions from flood irradiation data without imposing strict requirements on the spatial uniformity of the event distribution. A successful application of the method for medical gamma cameras is demonstrated using both simulated and experimental data. An implementation of the iterative reconstruction technique capable of operating in real time is presented. We show that this technique can also be used for monitoring photomultiplier gain variations.

Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d_1/e) were able to characterize the whole blood coagulation process in contrast to existing optical tests that are performed on plasma samples. To evaluate the feasibility of the technique for quantifying the effect of fibrinogen (Fbg) on blood coagulation, a dynamic study of d_1/e of blood in various Fbg concentrations was performed in static state. Two groups of blood samples of hematocrit (HCT) in 35, 45, and 55% were reconstituted of red blood cells with: 1) treated plasma with its intrinsic Fbg removed and commercial Fbg added (0–8 g L⁻¹); and 2) native plasma with commercial Fbg added (0–8 g L⁻¹). The results revealed a typical behavior due to coagulation induced by calcium ions and the clotting time is Fbg concentration-dependent. The clotting time was decreased by the increasing amount of Fbg in both groups. Besides, the blood of lower HCT with various levels of Fbg took shorter time to coagulate than that of higher HCT. Consequently, the OCT method is a useful and promising tool for the detection of blood-coagulation processes induced with different Fbg levels.

Irradiation with protons and light ions offers new possibilities for tumor therapy but has a strong need for novel imaging modalities for treatment verification. The development of new detector systems, which can provide an in vivo range assessment or dosimetry, requires an accurate knowledge of the secondary radiation field and reliable Monte Carlo simulations. This paper presents multiple measurements to characterize the prompt γ-ray emissions during proton irradiation and benchmarks the latest Geant4 code against the experimental findings. Within the scope of this work, the total photon yield for different target materials, the energy spectra as well as the γ-ray depth profile were assessed. Experiments were performed at the superconducting AGOR cyclotron at KVI-CART, University of Groningen. Properties of the γ-ray emissions were experimentally determined. The prompt γ-ray emissions were measured utilizing a conventional HPGe detector system (Clover) and quantitatively compared to simulations. With the selected physics list QGSP_BIC_HP, Geant4 strongly overestimates the photon yield in most cases, sometimes up to 50%. The shape of the spectrum and qualitative occurrence of discrete γ lines is reproduced accurately. A sliced phantom was designed to determine the depth profile of the photons. The position of the distal fall-off in the simulations agrees with the measurements, albeit the peak height is also overestimated. Hence, Geant4 simulations of prompt γ-ray emissions from irradiation with protons are currently far less reliable as compared to simulations of the electromagnetic processes. Deviations from experimental findings were observed and quantified. Although there has been a constant improvement of Geant4 in the hadronic sector, there is still a gap to close.

We investigate the question of how the blob approach is related to tube of response based modelling of the system matrix. In our model, the tube of response (TOR) is approximated as a cylinder with constant density (TOR-CD) and the cubic voxels are replaced by spheres. Here we investigate a modification of the TOR model that makes it effectively equivalent to the blob model, which models the intersection of lines of response (LORs) with radially variant basis functions ('blobs') replacing the cubic voxels. Implications of the achieved equivalence regarding the necessity of final resampling in blob-based reconstructions are considered. We extended TOR-CD to a variable density tube model (TOR-VD) that yields a weighting function (defining all system matrix elements) which is essentially identical to that of the blob model. The variable density of TOR-VD was modelled by a Gaussian and a Kaiser–Bessel function, respectively. The free parameters of both model functions were determined by fitting the corresponding weighting function to the weighting function of the blob model. TOR-CD and the best-fitting TOR-VD were compared to the blob model with a final resampling step (BLOB-RS) and without resampling (BLOB-NRS) in phantom studies. For three different contrast ratios and two different voxel sizes, resolution noise curves were generated. TOR-VD and BLOB-NRS lead to nearly identical images for all investigated contrast ratios and voxel sizes. Both models showed strong Gibbs artefacts at 4 mm voxel size, while at 2 mm voxel size there were no Gibbs artefacts visible. The spatial resolution was similar to the resolution with TOR-CD in all cases. The resampling step removed most of the Gibbs artefacts and reduced the noise level but also degraded the spatial resolution substantially. We conclude that the blob model can be considered just as a special case of a TOR-based reconstruction. The latter approach provides a more natural description of the detection process and allows for modifications that are not readily representable within the blob framework.

The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images obtained by the dual-energy subtraction technique. This study was performed to evaluate the usefulness of bone suppression image processing in image-guided radiation therapy. We demonstrated the improved accuracy of markerless motion tracking on bone suppression images. Chest fluoroscopic images of nine patients with lung nodules during respiration were obtained using a flat-panel detector system (120 kV, 0.1 mAs/pulse, 5 fps). Commercial bone suppression image processing software was applied to the fluoroscopic images to create corresponding bone suppression images. Regions of interest were manually located on lung nodules and automatic target tracking was conducted based on the template matching technique. To evaluate the accuracy of target tracking, the maximum tracking error in the resulting images was compared with that of conventional fluoroscopic images. The tracking errors were decreased by half in eight of nine cases. The average maximum tracking errors in bone suppression and conventional fluoroscopic images were 1.3   ±   1.0 and 3.3   ±   3.3 mm, respectively. The bone suppression technique was especially effective in the lower lung area where pulmonary vessels, bronchi, and ribs showed complex movements. The bone suppression technique improved tracking accuracy without special equipment and implantation of fiducial markers, and with only additional small dose to the patient. Bone suppression fluoroscopy is a potential measure for respiratory displacement of the target.