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Two new bisphosphonates have been examined for their ability to bind 188Re and deliver it selectively to bone. The bisphosphonates are prototype compounds with potential to deliver rhenium radionuclides and a second therapy modality to bone metastases. A conjugate between diethylenetriaminepentaacetic acid and bisphosphonate (DTPA/BP) and a conjugate between 5-fluorouracil and bisphosphonate (5-FU/BP) were prepared and labeled at high radiochemical purity with 188Re and biodistribution studies were carried out in normal Balb/C mice. The compounds showed rapid blood clearance and elimination from soft tissues with substantial retention of activity in the bone comparable to 188Re-hydroxyethylidine diphosphonate used as a control. At 8 h bone activity was 3.51% of injected dose for 188Re-DTPA/BP and 6.38% of injected dose for 188Re-5-FU/BP representing 69.6% and 80.6% of total body radioactivity, respectively. The two compounds show the potential for combination therapy of painful bone metastases.

A single diffusion MRI streamline fiber tracking dataset may contain hundreds of thousands, and often millions of streamlines and can take up to several gigabytes of memory. This amount of data is not only heavy to compute, but also difficult to visualize and hard to store on disk (especially when dealing with a collection of brains). These problems call for a fiber-specific compression format that simplifies its manipulation. As of today, no fiber compression format has yet been adopted and the need for it is now becoming an issue for future connectomics research. In this work, we propose a new compression format, .zfib, for streamline tractography datasets reconstructed from diffusion magnetic resonance imaging (dMRI). Tracts contain a large amount of redundant information and are relatively smooth. Hence, they are highly compressible. The proposed method is a processing pipeline containing a linearization, a quantization and an encoding step. Our pipeline is tested and validated under a wide range of DTI and HARDI tractography configurations (step size, streamline number, deterministic and probabilistic tracking) and compression options. Similar to JPEG, the user has one parameter to select: a worst-case maximum tolerance error in millimeter (mm). Overall, we find a compression factor of more than 96% for a maximum error of 0.1mm without any perceptual change or change of diffusion statistics (mean fractional anisotropy and mean diffusivity) along bundles. This opens new opportunities for connectomics and tractometry applications.

Oxygenation-sensitive (OS) cardiovascular magnetic resonance (CMR) is used to noninvasively measure myocardial oxygenation changes during pharmacologic vasodilation. The use of breathing maneuvers with OS CMR for diagnostic purposes has been recently proposed based on the vasodilatory effect of Co2, which can be enhanced by the additive effect of mild hypoxia. This study seeks to investigate this synergistic concept on coronary arteriolar resistance with OS CMR. In nine anesthetized swine, normoxemic and mild hypoxemic arterial partial pressure of oxygen (Pao2) levels (100 and 80 mmHg) were targeted with three arterial partial pressure of carbon dioxide (Paco2) levels of 30, 40, and 50 mmHg. During a 60-sec apnea from the set baselines, OS T2*-weighted gradient echo steady-state free precession (SSFP) cine series were obtained in a clinical 1.5T magnetic resonance imaging (MRI) system. Arterial blood gases were acquired prior to and after apnea. Changes in global myocardial signal intensity (SI) were measured. Although a greater drop in arterial oxygen saturation (SaO2) was observed in the hypoxemic baselines, myocardial SI increased or was maintained during apnea in all levels (n = 6). An observed decrease in left ventricular blood pool SI was correlated with the drop in SaO2. Corrected for the arterial desaturation, the calculated SI increase attributable to the increase in myocardial blood flow was greater in the hypoxemic levels. Both the changes in Paco2 and Pao2 were correlated with myocardial SI changes at normoxemia, yet not at hypoxemic levels. Using OS CMR, we found evidence that myocardial oxygenation is preserved during hypoxia when combined with Co2-increasing maneuvers, indicating synergistic effects of hypoxemia and hypercapnia on myocardial blood flow.

Transcatheter placement of left atrial closure device is an attractive therapy for patients with atrial fibrillation (AF), to avoid anticoagulation and reduce cerebrovascular events; however peri-device leaks occur. The geometry of the left atrial appendage (LAA) is not well understood, largely owing to limitations of 2-dimensional imaging techniques. We sought to better define the LAA orifice geometry, by performing 3-dimensional multi-detector computed tomography measurements. We prospectively recruited 105 consecutive patients referred for pulmonary vein ablation (PVA) and age-matched controls. Area, short and long-axis measurements were performed. Eccentricity was calculated as 1-(short axis/long axis). Multiple clinical variables were tested for their ability to predict appendage orifice eccentricity using univariate linear regression models. The PVA cohort demographics included; 25 (24 %) females, mean age 59 years (SD = 10), median height (1.55–2.03), weight 89 (56–139) kg and body surface area 2.1 (1.61–2.58). In the PVA cohort, there was a significant difference between the long and short-axis; median short-axis dimension was 20.5 (12.9–35.4) mm, versus long-axis median 30.4 (17.7–43.8) (p < 0.001). Mean eccentricity score was 0.4. When compared with controls, there was a significant difference in the short and long-axis measurements (p < 0.001) as well as eccentricity (p = 0.04). All clinical variables tested showed limited ability to predict appendage eccentricity (p = NS). LAA ostium is an elliptical structure in the setting of AF with a high eccentricity index and uniformly significant differences between short and long-axis. There were significant differences between these parameters when compared with controls. A deeper appreciation of LAA geometry and eccentricity may allow for reduction in peri-closure leaks.

Leukocyte-endothelial interactions within the microvasculature represent a hallmark of inflammation regardless of whether the inflammation results from non-infectious or infectious triggers. In this review, we highlight features of leukocyte recruitment in ocular disease and postulate mechanisms by which the infiltrating cells may lead to the progression of the ocular inflammatory response, including cytokine and chemokine production, T cell or non-T cell responses. Additionally, ex-vivo and in vivo methods used to study the general features of the immune response are discussed, with a specific focus on intravital imaging, which allows real-time non-invasive examination of leukocyte-endothelial interactions in the ocular microvasculature. At the present time there are still significant gaps in our understanding of the process of leukocyte recruitment in vivo in different microvascular beds. Further studies using non-invasive imaging approaches, such as intravital microscopy, provide an opportunity to study dynamic tissue-specific leukocyte-endothelial interactions in vivo and identify novel targets for early intervention in the inflammatory process. This knowledge is essential to the rational use of therapeutics to resolve inflammation in ocular disease.

Aims Cardiac computed tomography (CT) measured coronary artery calcium (CAC-CT) is a well-validated and accurate tool for estimating atherosclerotic burden and prognosis. Computed tomography attenuation correction (ACCT) obtained during cardiac positron emission tomography (PET) has been used to visually estimate CAC; however, quantification using a non-gated ACCT images has not been described. We sought to understand the relationship between CAC measured using cardiac computed tomography (CT) and CAC using ACCT images obtained during cardiac PET perfusion imaging. Methods and results Patients with both CAC-CT and cardiac PET within 6 months of each other were identified. CAC-CT images were scored using the Agatston scoring method, while ACCT images were scored using different attenuation thresholds for calcium. CAC-CT and ACCT scores were compared. Between August 2007 and October 2010, 91 patients were included in the analysis. Interobsever reliability was excellent at all thresholds of detection tested. Pearson correlation was strongest between CAC-CT and ACCT at 50 HU threshold of detection (ACCT50). Implementing CAC categories (0, 1–100, 101–400, >400), there was a high degree of agreement between observers as well as between CAC-CT and ACCT50. Correlation was best for lower CAC scores; however, as CAC-CT increased, ACCT50 underestimated CAC. Conclusion Quantifying CAC using ACCT images appears to be feasible and accurate. In a single cardiac PET examination, information regarding perfusion, LV function, flow quantification, and CAC can be obtained without additional radiation.

Purpose Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize tumors with image guidance, and excellent local control.

AbstractBecause of its fast image acquisition and the rich diagnostic information it provides, computed tomography (CT) has gradually become a popular imaging modality among clinicians. Because CT scanners emit x-rays, the increased use of CT in clinical applications inevitably leads to increased medical radiation dose to the population. Because of the well-known cancer-inducing effects of high dose x-ray radiation, this increased dose has caused concerns among policy makers and general public that CT patients may be at a higher risk of developing cancer. Over the years, CT manufacturers have developed a variety of strategies to address this issue, the latest being a model-based iterative reconstruction (MBIR) algorithm. MBIR is an advanced CT algorithm that incorporates modeling of several key parameters that were omitted in earlier algorithms to reduce computational requirement and speed up scans. This review article examines the latest literature in the clinical CT field and discusses the general principles of MBIR, its dose and noise reduction potentials, its imaging characteristics, and its limitations. MBIR algorithm and its application in today's CT imaging will greatly reduce the radiation dose to patients and improve image quality for clinicians.

Abstract Purpose: To develop an evidence-based clinical practice guideline that would address the following questions: (a) What is the role of prophylactic cranial irradiation (PCI) in patients with limited or extensive stage small-cell lung cancer (SCLC) who have achieved complete remission in response to induction therapy (chemotherapy or chemoradiotherapy)? (b) What dose and fractionation schedules of PCI are optimal? (c) Does the use of PCI in patients with SCLC in complete remission affect quality of life? Survival, disease-free survival, quality of life, and adverse effects were the outcomes of interest. Methods and Materials: A systematic review of the published literature was undertaken to provide the data for an evidence-based practice guideline. Results: Six randomized controlled trials and one fully published individual patient data meta-analysis were included in the systematic review of the evidence. For patients who have achieved complete response after induction therapy, there is evidence of a disease-free survival benefit (4 of 6 trials) and an overall survival benefit (meta-analysis). There is insufficient evidence to make a definitive recommendation with respect to dose. There is some indication that 30–36 Gy in 2–3 Gy per fraction, or a biologically equivalent dose, may produce a better outcome than a lower dose or less aggressive fractionation regimen. The schedule commonly used in Canada is 25 Gy in 10 fractions over 2 weeks. Data from further research, including a trial currently ongoing that compares 25 Gy in 10 fractions with 36 Gy in 18 fractions, will be required to determine optimal dose of PCI. There is insufficient evidence to make recommendations concerning the optimal timing of PCI in relation to the administration of chemotherapy. Lung DSG members generally felt that it should be given as soon as possible after completion of chemotherapy. There is evidence from trials with data for up to 2 years of follow-up that prophylactic cranial irradiation does not produce significant late neurotoxicity. There is evidence from one trial that prophylactic cranial irradiation does not have a detrimental effect on quality of life in the first 12 months following the completion of therapy. There is insufficient evidence to comment on the long-term effects of prophylactic cranial irradiation on quality of life. Conclusion: For adult patients with limited or extensive SCLC who achieve a complete remission with induction therapy, PCI is recommended.