Spatiotemporal radiotherapy planning using a global optimization approach.

This paper aims at quantifying the extent of potential therapeutic gain, measured using biologically effective dose (BED), that can be achieved by altering the radiation dose distribution over treatment sessions in fractionated radiotherapy. To that end, a spatiotemporally integrated planning approach is developed, where the spatial and temporal dose modulations are optimized simultaneously. The concept of equivalent uniform BED (EUBED) is used to quantify and compare the clinical quality of spatiotemporally heterogeneous dose distributions in target and critical structures. This gives rise to a large-scale non-convex treatment-plan optimization problem, which is solved using global optimization techniques. The proposed spatiotemporal planning approach is tested on two stylized cancer cases resembling two different tumor sites and sensitivity analysis is performed for radio-biological and EUBED parameters. Numerical results validate that spatiotemporal plans are capable of delivering a larger BED to the target volume without increasing the BED in critical structures compared to conventional time-invariant plans. In particular, this additional gain is attributed to the irradiation of different regions of the target volume at different treatment sessions. Additionally, the trade-off between the potential therapeutic gain and the number of distinct dose distributions is quantified, which suggests a diminishing marginal gain as the number of dose distributions increases.

Investigation of DNA Damage Dose-Response Kinetics after Ionizing Radiation Schemes Similar to CT Protocols.

Although there has been extensive research done on the biological response to doses of ionizing radiation relevant to radiodiagnostic procedures, very few studies have examined radiation schemes similar to those frequently utilized in CT exams. Instead of a single exposure, CT exams are often made up of a series of scans separated on the order of minutes. DNA damage dose-response kinetics after radiation doses and schemes similar to CT protocols were established in both cultured (ESW-WT3) and whole blood lymphocytes and compared to higher dose exposures. Both the kinetics and extent of H2AX phosphorylation were found to be dose dependent. Damage induction and detection showed a clear dose response, albeit different, at all time points and differences in the DNA repair kinetics of ESW-WT3 and whole blood lymphocytes were characterized. Moreover, using a modified split-dose in vitro experiment, we show that phosphorylation of H2AX is significantly reduced after exposure to CT doses fractionated over a few minutes compared to the same total dose delivered as a single exposure. Because the split-dose exposures investigated here are more similar to those experienced during a CT examination, it is essential to understand why and how these differences occur. This work provides compelling evidence supporting differential biological responses not only between high and low doses, but also between single and multiple exposures to low doses of ionizing radiation.

Prevalence of coronary artery disease evaluated by coronary CT angiography in women with mammographically detected breast arterial calcifications.

To assess the correlation between breast arterial calcifications (BAC) on digital mammography and the extent of coronary artery disease (CAD) diagnosed with dual source coronary computed tomography angiography (CTA) in a population of women both symptomatic and asymptomatic for coronary artery disease. 100 consecutive women (aged 34 - 86 years) who underwent both coronary CTA and digital mammography were included in the study. Health records were reviewed to determine the presence of cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes mellitus, and smoking. Digital mammograms were reviewed for the presence and degree of BAC, graded in terms of severity and extent. Coronary CTAs were reviewed for CAD, graded based on the extent of calcified and non-calcified plaque, and the degree of major vessel stenosis. A four point grading scale was used for both coronary CTA and mammography. The overall prevalence of positive BAC and CAD in the studied population were 12% and 29%, respectively. Ten of the 12 patients with moderate or advanced BAC on mammography demonstrated moderate to severe CAD as determined by coronary CTA. For all women, the positive predictive value of BAC for CAD was 0.83 and the negative predictive value was 0.78. The presence of BAC on mammography appears to correlate with CAD as determined by coronary CTA (Spearman's rank correlation coefficient = 0.48, p<.000001). Using logistic regression, the inclusion of BAC as a feature in CAD predication significantly increased classification results (p=0.04).

Predictive plain X-ray findings in distinguishing early stage acute lymphoblastic leukemia from juvenile idiopathic arthritis.

Acute lymphoblastic leukemia (ALL) presenting with musculoskeletal pain may be difficult to distinguish from juvenile idiopathic arthritis (JIA). The objective of this study, which separates it from most studies investigating these two diseases, is to determine the role of plain radiography in the initial approach toward patients presenting with musculoskeletal symptoms and to look for signs suggestive of each of the two disease entities. X-rays of patients referred to our center for musculoskeletal symptoms and ultimately diagnosed with JIA or ALL over a period of 10 years were studied retrospectively. The X-rays had been performed in the preliminary stage of the disease process and before the initiation of specific therapeutic measures. Soft tissue swelling, osteopenia, radiolucent metaphyseal bands, coarse trabeculation, and periosteal reactions were studied, and data analysis was performed by SPSS. Among a total of 174 patients, 118 had been diagnosed with JIA and 56 with ALL. The average age of JIA patients and ALL patients were 7.5 and 7.2 years, respectively. Soft tissue swelling was significantly more common among JIA patients (89.8%) than among those with ALL (1.8%) (P < 0.0001). Therefore, it is of the utmost importance to note the presence or absence of soft tissue swelling on plain radiography in the initial diagnostic approach. Osteopenia was seen in 60.2% of JIA patients compared with 14.3% of ALL patients (P < 0.0001). Radiolucent metaphyseal bands were seen among 7.1% of ALL cases but were notably absent in all cases of JIA. Coarse trabeculation was significantly higher in patients with ALL (7.1% ) than among JIA patients (0.8%). Periosteal reactions were seen in 6.8% of JIA group compared with 1.8% of ALL patients. We concluded that plain X-ray may be useful in selecting patients requiring bone marrow examination among those presenting with musculoskeletal symptoms mimicking JIA.

Compensation of optical heterogeneity-induced artifacts in fluorescence molecular tomography: theory and in vivo validation.

We present a method for reduction of image artifacts induced by the optical heterogeneities of tissue in fluorescence molecular tomography (FMT) through identification and compensation of image regions that evidence propagation of emission light through thin or low-absorption tunnels in tissue. The light tunneled as such contributes to the emission image as spurious components that might substantially overwhelm the desirable fluorescence emanating from the targeted lesions. The proposed method makes use of the strong spatial correlation between the emission and excitation images to estimate the tunneled components and yield a residual image that mainly consists of the signal due to the desirable fluorescence. This residual image is further refined using a coincidence mask constructed for each excitation-emission image pair. The coincidence mask is essentially a map of the "hot spots" that occur in both excitation and emission images, as such areas are often associated with tunneled emission. In vivo studies are performed on a human colon adenocarcinoma xenograft tumor model with subcutaneous tumors and a murine breast adenocarcinoma model with aggressive tumor cell metastasis and growth in the lungs. Results demonstrate significant improvements in the reconstructions achieved by the proposed method.

Pathologic significance of the "dural tail sign".

OBJECTIVE: The exact nature of the "dural tail sign" (thickening of the dura adjacent to the tumour in contrast enhanced T1-MRI imaging) is still not clearly established. In this study we tried to verify the histological appearance of the "dural tail sign" and probable correlation between different MRI findings and dural tail histology. MATERIAL AND METHODS: In this study, 129 patients with intracranial lesions underwent MRI imaging with 1.5T scanner. The "dural tail sign" was defined using Goldsher et al. criteria. Size and pattern of enhancement of the tumour and adjacent dura was noted in MRI and in the pathologic samples, dural tail and the dura beneath the tumour was assessed. RESULTS: In 30 cases, "dural tail sign" was evident on MRI, dural tail noted in 17 of these cases in histological samples (12 meningiomas, 3 pituitary adenomas and 2 schwannomas). All of them had vessel dilatation, 6 showed tumoural invasion, 4 demonstrated intravascular growth of the lesion and 1 showed inflammation of the dura. CONCLUSION: In our study MRI findings failed to predict tumoural invasion of the dural tail in histologic samples and because of frequent presence of tumour nests in it, the dura matter should be resected as widely as possible.

Multifunctional and compact spectrometers based on cylindrical beam volume holograms.

We propose a new class of slitless spectrometers using cylindrical beam volume holograms. These holograms disperse an input beam in one direction in an output plane while they do not affect the beam in the perpendicular direction. We show that the spectral mapping of the input beam can be obtained in one direction and the beam can be independently modified in the perpendicular direction. Using this unique property, we demonstrate a spectral wrapping technique to considerably increase the operation spectral range of the slitless spectrometers, without sacrificing their resolution.