Parathyroid Hormone Resistance: An Uncommon Cause of Hypocalcaemia in an Adult Ghanaian Female.

BACKGROUND AND OBJECTIVE: Parathyroid hormone (PTH) resistance, the main biochemical feature of a rare group of disorders known as Pseudohypoparathyroidism (PHP) is an uncommon cause of hypocalcaemia. In addition to the biochemical abnormalities, some individuals with PHP may have features of Albright Hereditary Osteodystrophy (AHO). Being a rare disorder with a significant level of variation and overlap in its clinical presentation, diagnosis of PHP may be challenging in some clinical settings. This case report highlights the diagnosis of this rare disorder. CASE REPORT: A 20-year-old Ghanaian female who had been involved in a road traffic accident (RTA) was referred to the endocrine clinic after a computer tomography (CT) scan of her head revealed an incidental finding of multiple basal ganglia calcifications. Investigations revealed hypocalcaemia, hyperphosphatemia, and elevated intact PTH in the presence of normal levels of 25-hydroxyvitamin D and magnesium, and a normal kidney function. She also had phenotypic features of AHO. Findings suggested a diagnosis of PHP, however, the type could not be identified due to the unavailability of further testing. CONCLUSION: This report of a Ghanaian female with PTH resistance and features of AHO diagnosed at the age of 20 years, is expected to add to the existing literature and assist in increasing the level of awareness and facilitate the diagnosis of this disorder in our setting.

CONTEXTE ET OBJECTIF: La résistance à l'hormone parathyroïdienne (PTH), principale caractéristique biochimique d'un groupe rare de troubles connus sous le nom de pseudohypoparathyroïdie (PHP), est une cause rare d'hypocalcémie. En plus des anomalies biochimiques, certaines personnes atteintes de PHP peuvent présenter des caractéristiques d'ostéodystrophie héréditaire d'Albright (AHO). Étant un trouble rare avec un niveau significatif de variation et de chevauchement dans sa présentation clinique, le diagnostic de PHP peut être difficile dans certains contextes cliniques. Ce rapport de cas met en lumière le diagnostic de cette maladie rare. RAPPORT DE CAS: Une femme ghanéenne de 20 ans qui avait été impliquée dans un accident de la circulation routière (RTA) a été référée à la clinique endocrinienne après qu'une tomodensitométrie (TDM) de sa tête a révélé la découverte fortuite de multiples calcifications des ganglions de la base. Les examens ont révélé une hypocalcémie, une hyperphosphatémie et une PTH intacte élevée en présence de taux normaux de 25 hydroxyvitamine D et de magnésium et d'une fonction rénale normale. Elle avait également des caractéristiques phénotypiques d'AHO. La découverte a suggéré un diagnostic de PHP, mais le type n'a pas pu être identifié en raison de l'indisponibilité de tests supplémentaires. CONCLUSION: Ce rapport d'une femme ghanéenne présentant une résistance à la PTH et des caractéristiques d'AHO diagnostiquée à l'âge de 20 ans, devrait s'ajouter à la littérature existante et aider à accroître le niveau de sensibilisation et à faciliter le diagnostic de ce trouble dans notre contexte. Mots-clés: Hypocalcémie, Hormone parathyroïdienne, Ghana.

Determinants of willingness to accept kidney transplantation among chronic kidney disease patients in Ghana.

BACKGROUND: The burden of chronic kidney disease in Africa is three to four times higher compared to high-income countries and the cost of treatment is beyond the reach of most affected persons. The best treatment for end stage renal disease is kidney transplantation which is not available in most African countries. As kidney transplantation surgery is emerging in Ghana, this study assessed factors which could influence the willingness of patients with chronic kidney disease to accept it as a mode of treatment. METHODS: This cross-sectional survey was carried out among patients with chronic kidney disease in Korle-Bu Teaching Hospital. A consecutive sampling method was used to recruit consenting patients. A structured questionnaire and standardized research instruments were used to obtain information on demographic, socio-economic characteristics, knowledge about transplantation, perception of transplantation, religiosity and spirituality. Logistic regression model was used to assess the determinants of willingness to accept a kidney transplant. RESULTS: 342 CKD patients participated in the study of which 56.7% (n = 194) were male. The mean age of the participants was 50.24 ± 17.08 years. The proportion of participants who were willing to accept a kidney transplant was 67.3% (95%CI: 62.0-72.2%). The factors which influenced participants' willingness to accept this treatment included; willingness to attend a class on kidney transplantation (p < 0.016), willingness to donate a kidney if they had the chance (p < 0.005), perception that a living person could donate a kidney (p < 0.001) and perceived improvement in quality of life after transplantation (p < 0.005). The barriers for accepting kidney transplantation were anticipated complications of transplant surgery and financial constraints. CONCLUSION: More than two-thirds of CKD patients were willing to accept a kidney transplant and this is influenced by multiple factors. Government health agencies must consider full or partial coverage of kidney transplantation through the existing national health insurance scheme. Further, efficient educational programmes are required to improve both patients' and physicians' knowledge on the importance of kidney transplantation in the management of end stage renal disease in Ghana.

High BMI: an important health risk factor among older adults in Ghana.

OBJECTIVE: We examined BMI as a health risk factor for self-reported diabetes mellitus, angina, strokes and arthritis among older Ghanaians aged 50 years and above. DESIGN: We analysed the individual-level data from the World Health Organization Study on global AGEing and adult health Ghana Wave 2 (2014/2015). The influence of BMI on self-reported chronic conditions including diabetes, angina, stroke and arthritis was examined. SETTING: Households from all the administrative regions of Ghana. PARTICIPANTS: Included 3350 adults aged 50 years and older. RESULTS: The prevalence of overweight and obesity among participants was 22·8 % (95 % CI 20·6, 25·2) and 13·2 %, respectively (95 % CI 11·5, 15·1). With respect to individual chronic conditions, arthritis emerged with the highest prevalence rate of 7·3 (95 % CI 5·3, 9·9), while the prevalence rate of diabetes, angina and stroke was 2·8 % (95 % CI 2·0, 3·9), 1·7 % (95 % CI 1·1, 2·6) and 1·3 % (95 % CI 1·0, 1·8), respectively. The risk of diabetes among overweight and obesity was over three and two times, respectively, higher compared with participants with normal weights. Overweight and obesity were significantly more than two and three times likely to experience angina, respectively, compared with participants with normal weight. Obesity significantly influences arthritis with approximately two times increased odds compared with normal weight participants. CONCLUSION: Prevalence of obesity and overweight in Ghana is high and increasing, which poses a health risk at the individual and population levels. Inter-sectorial and multidisciplinary measures in line with the national non-communicable disease policies aimed at curbing this trend are imperative.

Willingness to pay for kidney transplantation among chronic kidney disease patients in Ghana.

BACKGROUND: Kidney transplantation is the preferred treatment for patients with end stage renal disease. However, it is largely unavailable in many sub-Sahara African countries including Ghana. In Ghana, treatment for end stage renal disease including transplantation, is usually financed out-of-pocket. As efforts continue to be made to expand the kidney transplantation programme in Ghana, it remains unclear whether patients with Chronic Kidney Disease (CKD) would be willing to pay for a kidney transplant. AIM: The aim of the study was to assess CKD patients' willingness to pay for kidney transplantation as a treatment option for end stage renal disease in Ghana. METHODS: A facility based cross-sectional study conducted at the Renal Outpatient clinic and Dialysis Unit of Korle-Bu Teaching Hospital among 342 CKD patients 18 years and above including those receiving haemodialysis. A consecutive sampling approach was used to recruit patients. Structured questionnaires were administered to obtain information on demographic, socio-economic, knowledge about transplant, perception of transplantation and willingness to pay for transplant. In addition, the INSPIRIT questionnaire was used to assess patients' level of religiosity and spirituality. Contingent valuation method (CVM) method was used to assess willingness to pay (WTP) for kidney transplantation. Logistic regression model was used to determine the significant predictors of WTP. RESULTS: The average age of respondents was 50.2 ± 17.1 years with most (56.7% (194/342) being male. Overall, 90 out of the 342 study participants (26.3%, 95%CI: 21.7-31.3%) were willing to pay for a kidney transplant at the current going price (≥ $ 17,550) or more. The median amount participants were willing to pay below the current price was $986 (IQR: $197 -$1972). Among those willing to accept (67.3%, 230/342), 29.1% (67/230) were willing to pay for kidney transplant at the prevailing price. Wealth quintile, social support in terms of number of family friends one could talk to about personal issues and number of family members one can call on for help were the only factors identified to be significantly predictive of willingness to pay (p-value < 0.05). CONCLUSION: The overall willingness to pay for kidney transplant is low among chronic kidney disease patients attending Korle-Bu Teaching Hospital. Patients with higher socio-economic status and those with more family members one can call on for help were more likely to pay for kidney transplantation. The study's findings give policy makers an understanding of CKD patients circumstances regarding affordability of the medical management of CKD including kidney transplantation. This can help develop pricing models to attain an ideal poise between a cost effective but sustainable kidney transplant programme and improve patient access to this ultimate treatment option.

Knowledge and Willingness to Donate Kidneys for Transplantation in Ghana: A Cross-Sectional Survey.

BACKGROUND: The main treatment modalities for chronic kidney disease (CKD) are dialysis and kidney transplantation. While kidney transplantation provides better survival and quality of life outcomes, it is a new treatment option in Ghana. Finding kidney donors for transplant may be a major challenge due to varied views of the public. METHODS: This cross-sectional study was carried out in 5 purposively selected communities in the Greater Accra region in Ghana. Structured questionnaires and standardized instruments were used to assess sociodemographic characteristics, spirituality, and perception of kidney transplantation. RESULTS: The mean age of the 480 participants was 29.60 ± 10.65 years. The proportion of men was 51%. The average score for knowledge of participants on kidney donation was 4.8 ± 2.6. The level of spirituality score was 25.4 ± 3.89. Approximately 48% (231/480) of participants were willing to donate a kidney while still alive. Willingness to donate when dead was 72% (344/480). Willingness to donate a kidney when dead was significantly lower among the participants in the older age groups. High level of knowledge about kidney transplantation, being employed, basic formal education, and never married were associated with willingness to donate kidney (P < .05). CONCLUSION: Our results suggest that participants have a low level of knowledge regarding kidney transplantation, while about two-thirds are willing to donate only after death. Continuous public education is key to raise public awareness of the need for kidney transplants. This will support the Ministry of Health in their efforts to institute a kidney transplant program in Ghana.

Toward personalized dose-prescription in locally advanced non-small cell lung cancer: Validation of published normal tissue complication probability models.

PURPOSE: To identify published normal tissue complication probability (NTCP) models suitable for patient-specific dose-prescription in locally advanced non-small cell lung cancer (LA-NSCLC) through in-house validation. MATERIAL AND METHODS: From eight previously published candidate NTCP models (≥grade 2 acute esophagitis and radiation pneumonitis; AE2, RP2), patient-specific dose-responses were calculated using model variables and fractionation-corrected doses for 241 LA-NSCLC patients treated with chemo-IMRT to 50-80 Gy@1.8-2.0 Gy between 2004 and 2014 (AE2/RP2 rate: 50%/12%). A model was judged final if it significantly predicted AE2 or RP2 (p ≤ 0.05), was discriminative and well calibrated (AUC > 0.60; Hosmer-Lemeshow test pHL > 0.05), which were assessed as the median over 1000 bootstrap samples. RESULTS: Models for AE2 had superior discrimination to RP2 models (AUC = 0.63-0.65 vs. 0.51-0.65). The final AE2 model included mean esophageal dose and concurrent chemotherapy (AUC = 0.65; p < 0.0001). The final RP2 model was a slightly adjusted version of the RP2 model with the best discrimination, and included age, mean lung dose, and pulmonary comorbidity (AUC = 0.73; p < 0.0001). CONCLUSION: Of the eight investigated and published NTCP models, one model successfully described AE2 and one slightly adjusted model successfully described RP2 in the independent cohort. Estimates from these two NTCP models will, therefore, be considered internally when prescribing patient-specific doses in LA-NSCLC patients.

Radiotherapeutic implications of the updated ICRP thresholds for tissue reactions related to cataracts and circulatory diseases.

Radiation therapy of cancer patients involves a trade-off between a sufficient tumour dose for a high probability of local control and dose to organs at risk that is low enough to lead to a clinically acceptable probability of toxicity. The International Commission on Radiological Protection (ICRP) reviewed epidemiological evidence and provided updated estimates of 'practical' threshold doses for tissue injury, as defined at the level of 1% incidence, in ICRP Publication 118. Particular attention was paid to cataracts and circulatory diseases. ICRP recommended nominal absorbed dose threshold for these outcomes as low as 0.5 Gy. Threshold doses for tissue reactions can be reached in some patients during radiation therapy. Modern treatment planning systems do not account for such low doses accurately, and doses to therapy patients from associated imaging procedures are not generally accounted for. While local control is paramount, the observations of ICRP Publication 118 suggest that radiation therapy plans and processes should be examined with particular care. The research needs are discussed in this paper.

Predictors and outcome of systemic lupus erythematosus (SLE) admission rates in a large teaching hospital in sub-Saharan Africa.

Although it was previously believed that systemic lupus erythematosus was uncommon among Africans, it has become increasingly apparent that the incidence is higher, and socioeconomic challenges such as physician shortages, poor medical facility access, and poor health literacy may worsen prognosis. This retrospective study examines characteristics and outcomes of hospitalized systemic lupus erythematosus patients over a two-year period and serves as a baseline for comparison for future studies to examine the outcomes with the provision of more dedicated care. There were 51 patient admissions over a two-year period, with a mean duration from start of illness to admission of approximately two years. Duration of admission ranged from one to 140 days with a mean period of 26.12 days (SD ± 26.6). There were 22 deaths (43.1% of admissions), which were mainly due to infections and renal complications. Factors associated with risk of death in regression analysis were: infections, fever, disease flare, musculoskeletal involvement, amenorrhea, depression, a clinical finding of hepatomegaly, and chest infection. Understanding the effect and outcome of systemic lupus erythematosus across different countries can elucidate the role of genetic, environmental, and other causative factors in the progression of the disease.

A study of respiration-correlated cone-beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer.

PURPOSE: There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone. A second study goal compares respiration-correlated vs respiration-averaged images for determining tumor deviations. METHODS: Eleven stage II-IV nonsmall cell lung cancer patients are enrolled in an IRB-approved prospective off-line protocol using RC-CBCT guidance to correct for systematic errors in GTV position. Patients receive a respiration-correlated planning CT (RCCT) at simulation, daily kilovoltage RC-CBCT scans during the first week of treatment and weekly scans thereafter. Four types of correction methods are compared: (1) systematic error in gross tumor volume (GTV) position, (2) systematic error in skeletal anatomy, (3) daily skeletal corrections, and (4) weekly skeletal corrections. The comparison is in terms of weighted average of the residual GTV deviations measured from the RC-CBCT scans and representing the estimated residual deviation over the treatment course. In the second study goal, GTV deviations computed from matching RCCT and RC-CBCT are compared to deviations computed from matching respiration-averaged images consisting of a CBCT reconstructed using all projections and an average-intensity-projection CT computed from the RCCT. RESULTS: Of the eleven patients in the GTV-based systematic correction protocol, two required no correction, seven required a single correction, one required two corrections, and one required three corrections. Mean residual GTV deviation (3D distance) following GTV-based systematic correction (mean ± 1 standard deviation 4.8 ± 1.5 mm) is significantly lower than for systematic skeletal-based (6.5 ± 2.9 mm, p = 0.015), and weekly skeletal-based correction (7.2 ± 3.0 mm, p = 0.001), but is not significantly lower than daily skeletal-based correction (5.4 ± 2.6 mm, p = 0.34). In two cases, first-day CBCT images reveal tumor changes-one showing tumor growth, the other showing large tumor displacement-that are not readily observed in radiographs. Differences in computed GTV deviations between respiration-correlated and respiration-averaged images are 0.2 ± 1.8 mm in the superior-inferior direction and are of similar magnitude in the other directions. CONCLUSIONS: An off-line protocol to correct GTV-based systematic error in locally advanced lung tumor cases can be effective at reducing tumor deviations, although the findings need confirmation with larger patient statistics. In some cases, a single cone-beam CT can be useful for assessing tumor changes early in treatment, if more than a few days elapse between simulation and the start of treatment. Tumor deviations measured with respiration-averaged CT and CBCT images are consistent with those measured with respiration-correlated images; the respiration-averaged method is more easily implemented in the clinic.

SU-E-J-67: A Potential New Technique to Measure Respiratory Tidal Volume Using Optical Surface Imaging: A Geometric and Deformable Phantom Study.

PURPOSE: To develop a new method for accurate measurement of dynamic respiratory tidal volume, we investigate the feasibility of measuring torso volume change using optical surface imaging (OSI). METHODS: Based on a validated volume conservation theory, the tidal volume is equal to the volume change of the torso during quiet respiration (Li et al, PMB, 54:1693, 2009). A clinical OSI system was employed to acquire surface images of seven geometric phantoms and two 'deformable' torso phantoms. The mesh surface images were converted into contours for volume calculation using a treatment planning system. For geometric phantoms, their volumes under the incomplete surface images were calculated with aid of their symmetry. The results were compared with theoretical calculation and water containment experiments. For deformable torso phantoms, we created volume-controlled deformation stages by placing deformable PlayDoh (DPD) materials on top of rigid Rando/Thorax phantoms, mimicking respiration-induced torso surface elevation and volume change. The volume difference under the surfaces with and without the DPD padding was calculated with aid of a common posterior line to enclose the region of interest. Three different volumes of DPD padding (>500cc) were mounted on the torso phantoms and CT scanned for volume measurements. RESULTS: For geometric phantoms, the OSI measured volume had accuracy (±1s) of 0.0%±1.6% (vs. geometric volume calculation) and 0.6%±3.8% (vs. water containment experiment). For deformable torso phantoms, the volume change was measured using OSI with an accuracy of 1.5%±2.5% against the measured volume using CT imaging. Linear regression showed a one-to-one relationship between the OSI volumes and CT volumes with a slope of 1.003 (r2=0.999). CONCLUSIONS: The optical surface imaging system can accurately measure the volume of geometric phantoms and the volume change of deformable torso phantoms. The accuracy is about 3% against standard volume measurement methods. Further study on human subjects is under investigation. Memorial Sloan-Kettering Cancer Center has a reserach agreement with Vision RT, Inc.

SU-E-J-119: Comparative Evaluation of Respiratory Motion-Corrected Cone-Beam CT Images Derived from Treatment-Day Vs. Simulation-Day Respiration-Correlated CT Scans.

PURPOSE: Respiration-induced motion artifacts in cone-beam CT (CBCT) can be corrected using a model of patient motion obtained from respiration-correlated CT (RCCT). This approach assumes that respiration-induced organ deformations at simulation, when RCCT scans are normally acquired, are still valid at treatment. The purpose of this study is to compare lung tumor image quality in motion-corrected CBCT images derived from treatment-day RCCT(tx) to simulation-day RCCT(sim) patient images. METHODS: In an IRB-approved study, lung cancer patients receive an RCCT at simulation, and an RCCT, gated CBCT and 1-minute CBCT at one treatment session. CBCT projections from the 1-minute scan are sorted according to breathing amplitude from an external monitor and reconstructed and warped to obtain a motion-corrected MC-CBCT at end expiration. Motion correction uses a model adapted from either RCCT(tx) or RCCT(sim), thus obtaining MC-CBCT(tx) and MC-CBCT(sim) images respectively. A gated CBCT, in which gantry rotation and projection acquisition occur within a gate at end expiration, serves as ground truth for comparison. Quality of MC-CBCT images is evaluated from tumor-to-background contrast ratio (TBCR) values measured by delineating the tumor and annular volume around it on the gated CBCT then transferring the contours and aligning them to each MC-CBCT. RESULTS: TBCR is found tobe lower in MC-CBCT(sim) images, relative to MC-CBCT(tx), in four out of five patients with mean 21% reduction in a range 9-39%. In the remaining case, where there was no change in TBCR, tumor motion observed in the RCCT was small (2mm). Tumor motion extent relative to diaphragm is observed to change between RCCT(tx) and RCCT(sim) scans. CONCLUSIONS: Preliminary results indicate that deformation patterns in lung do change between simulation and treatment. Such variations may reduce the validity of using simulation data for motion-corrected CBCT at treatment. The findings require confirmation with larger numbers of patients. NIH/NCI award R01 CA126993, research grant from Varian Medical Systems.

SU-E-T-595: Comparison of Volumetric Modulated Arc Therapy (VMAT) and Static Intensity Modulated Radiotherapy (IMRT) for Malignant Pleural Mesothelioma in Patients with Intact Lungs/Post Pleurectomy.

PURPOSE: This planning study compares VMAT and static gantry, sliding window IMRT for malignant pleural mesothelioma for post pleurectomy. METHODS: We compared plans for a left sided (L) and a right sided case (R). Plans used clinically approved planning target volumes (PTVs) and critical organ contours. IMRT plans employed 7-8 6 MV photon beam directions over a 215° range centered on the ipsilateral lung. VMAT plans used 4 partial arcs within the same range and energy. Prescription dose per fraction was 1.8 Gy; case L went to 50.4 Gy, case R to 46.8 Gy. Planning objectives were: Lyman model NTCP for both lungs < 25%; contralateral lung, mean dose < 8 Gy; heart, V30 Gy < 50%, mean < 30 Gy; Each Kidney, V18 Gy < 33%; liver_not_GTV, mean < 30 Gy, V30 Gy < 50%; stomach not PTV, mean < 30 Gy; cord maximum < 45 Gy; bowel maximum < 55 Gy, D05 < 45 Gy; PTV D95 = 94%, V95 = 94%, D05 = 115%. Dose calculation was done with the AAA algorithm. RESULTS: VMAT and IMRT both met the dosimetric constraints. The VMAT MU were 887 (L)_and 896 (R) and for IMRT were 1691 (L) and 2409 (R). IMRT required 14-16 fields (wide-field splitting). The delivery times were 8 minutes (VMAT) and 20 minutes (IMRT). For coverage and plan homogeneity parameters within 1.5% - 2%, VMAT better spared organs at risk. CONCLUSIONS: Both VMAT and IMRT are feasible techniques for the treatment of malignant pleural mesothelioma with intact lungs, with less MU and a shorter delivery time for VMAT. Additional cases must be planned to test generality of our preliminary results.

SU-E-T-532: Comparison of Dose Distributions Calculated Using Different Planning Systems with Radiochromic Film Measurements in an Inhomogeneous Phantom.

PURPOSE: Accurate modeling of the dose distribution in a lung tumor is challenging for traditional dose calculation algorithms. We compare the dose distributions of four commercial dose calculation Methods: Raysearch (Raysearch Laboratories) and Pinnacle (Philips Healthcare) collapsed cone, and Eclipse AAA and Eclipse Acuros,(Varian Medical Systems) with measurements using radiochromic film in a lung tumor phantomMethods: A simple lung tumor phantom was constructed using a thermoplastic cylinder 29 mm diameter and 40mm in length (density 1.3 gm/cc) imbedded in cork phantom 25 × 25 × 20 cm of density 0.32 gm/cc. Nine film layers normal to the axis of the cylinder where placed between layers of cork, above, below and through the cylindrical inhomogeneity. The phantom was irradiated with a single asymmetric 10×10 cm 6 MV field with the central axis collinear with the cylinder axis. Thirteen film exposures at 5 cm depth taken with doses 0-10 Gy were used to calibrate the film. The phantom was CT scanned and the DICOM study loaded into each of the treatment planning systems to calculate the dose distribution in the phantom. RESULTS: Away from cork-poly interfaces, agreement between the four algorithms was within 3% of the film measurements. For Acuros, the dose at the edge of the cylinder was found to be up to 2% lower than that at the center of the cylinder possibly because of the loss of lateral electron equilibrium. CONCLUSIONS: All four algorithms achieved remarkable agreement with the radiochromic film measurement. The Acuros algorithm appeared to more accurately model the peripheral dose deficit in the tumor, although a more detailed study is required for confirmation.

Phase and amplitude binning for 4D-CT imaging.

We compare the consistency and accuracy of two image binning approaches used in 4D-CT imaging. One approach, phase binning (PB), assigns each breathing cycle 2pi rad, within which the images are grouped. In amplitude binning (AB), the images are assigned bins according to the breathing signal's full amplitude. To quantitate both approaches we used a NEMA NU2-2001 IEC phantom oscillating in the axial direction and at random frequencies and amplitudes, approximately simulating a patient's breathing. 4D-CT images were obtained using a four-slice GE Lightspeed CT scanner operating in cine mode. We define consistency error as a measure of ability to correctly bin over repeated cycles in the same field of view. Average consistency error mue+/-sigmae in PB ranged from 18%+/-20% to 30%+/-35%, while in AB the error ranged from 11%+/-14% to 20%+/-24%. In PB nearly all bins contained sphere slices. AB was more accurate, revealing empty bins where no sphere slices existed. As a proof of principle, we present examples of two non-small cell lung carcinoma patients' 4D-CT lung images binned by both approaches. While AB can lead to gaps in the coronal images, depending on the patient's breathing pattern, PB exhibits no gaps but suffers visible artifacts due to misbinning, yielding images that cover a relatively large amplitude range. AB was more consistent, though often resulted in gaps when no data existed due to patients' breathing pattern. We conclude AB is more accurate than PB. This has important consequences to treatment planning and diagnosis.

Reduction of organ motion effects in IMRT and conformal 3D radiation delivery by using gating and tracking techniques.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumour sites affected by respiratory motion such as lung, breast and liver tumours. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart) is expected. Four main strategies are used to reduce respiratory motion effects: integration of respiratory movements into treatment planning, breath-hold techniques, respiratory gating techniques, and tracking techniques. Measurements of respiratory movements can be performed either in a representative sample of the general population, or directly on the patient before irradiation. The measured amplitude could be applied to a geometrical margin or integrated into dosimetry. However, these strategies remain limited for very mobile tumours, in which this approach results in larger irradiated volumes. Reduction of breathing motion can be achieved by using either breath-hold techniques or respiration synchronized gating techniques. Breath-hold can be achieved with active techniques, in which a valve temporarily blocks airflow of the patient, or passive techniques, in which the patient voluntarily breath-holds. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. Another category is tumour tracking, which consists of two major aspects: real-time localization of, and real-time beam adaptation to, a constantly moving tumour. These techniques are presently being investigated in several medical centres worldwide. Although promising, the first results obtained in lung and liver cancer patients require confirmation. This paper describes the most frequently used gating and tracking techniques and the main published clinical reports.

Evaluation of an automated deformable image matching method for quantifying lung motion in respiration-correlated CT images.

We have evaluated an automated registration procedure for predicting tumor and lung deformation based on CT images of the thorax obtained at different respiration phases. The method uses a viscous fluid model of tissue deformation to map voxels from one CT dataset to another. To validate the deformable matching algorithm we used a respiration-correlated CT protocol to acquire images at different phases of the respiratory cycle for six patients with nonsmall cell lung carcinoma. The position and shape of the deformable gross tumor volumes (GTV) at the end-inhale (EI) phase predicted by the algorithm was compared to those drawn by four observers. To minimize interobserver differences, all observers used the contours drawn by a single observer at end-exhale (EE) phase as a guideline to outline GTV contours at EI. The differences between model-predicted and observer-drawn GTV surfaces at EI, as well as differences between structures delineated by observers at EI (interobserver variations) were evaluated using a contour comparison algorithm written for this purpose, which determined the distance between the two surfaces along different directions. The mean and 90% confidence interval for model-predicted versus observer-drawn GTV surface differences over all patients and all directions were 2.6 and 5.1 mm, respectively, whereas the mean and 90% confidence interval for interobserver differences were 2.1 and 3.7 mm. We have also evaluated the algorithm's ability to predict normal tissue deformations by examining the three-dimensional (3-D) vector displacement of 41 landmarks placed by each observer at bronchial and vascular branch points in the lung between the EE and EI image sets (mean and 90% confidence interval displacements of 11.7 and 25.1 mm, respectively). The mean and 90% confidence interval discrepancy between model-predicted and observer-determined landmark displacements over all patients were 2.9 and 7.3 mm, whereas interobserver discrepancies were 2.8 and 6.0 mm. Paired t tests indicate no significant statistical differences between model predicted and observer drawn structures. We conclude that the accuracy of the algorithm to map lung anatomy in CT images at different respiratory phases is comparable to the variability in manual delineation. This method has therefore the potential for predicting and quantifying respiration-induced tumor motion in the lung.

Quantitation of respiratory motion during 4D-PET/CT acquisition.

We report on the variability of the respiratory motion during 4D-PET/CT acquisition. The respiratory motion for five lung cancer patients was monitored by tracking external markers placed on the abdomen. CT data were acquired over an entire respiratory cycle at each couch position. The x-ray tube status was recorded by the tracking system, for retrospective sorting of the CT data as a function of respiration phase. Each respiratory cycle was sampled in ten equal bins. 4D-PET data were acquired in gated mode, where each breathing cycle was divided into ten 500 ms bins. For both CT and PET acquisition, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to their respiratory phases. The respiratory periods, and average amplitude within each phase bin, acquired in both modality sessions were then analyzed. The average respiratory motion period during 4D-CT was within 18% from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in the duration of each 4D-CT bin. This small uncertainty enabled good correlation between CT and PET data, on a phase-to-phase basis. Comparison of the average-amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by-bin basis show a maximum deviation of approximately 15%. This study has proved the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in most cases consistent between PET and CT sessions, thereby improving both the attenuation correction of PET images, and co-registration of PET and CT images. On the other hand, in two patients, there was an increased partial irregularity in their breathing motion, which would prevent accurately correlating the corresponding PET and CT images.

Four-dimensional (4D) PET/CT imaging of the thorax.

We have reported in our previous studies on the methodology, and feasibility of 4D-PET (Gated PET) acquisition, to reduce respiratory motion artifact in PET imaging of the thorax. In this study, we expand our investigation to address the problem of respiration motion in PET/CT imaging. The respiratory motion of four lung cancer patients were monitored by tracking external markers placed on the thorax. A 4D-CT acquisition was performed using a "step-and-shoot" technique, in which computed tomography (CT) projection data were acquired over a complete respiratory cycle at each couch position. The period of each CT acquisition segment was time stamped with an "x-ray ON" signal, which was recorded by the tracking system. 4D-CT data were then sorted into 10 groups, according to their corresponding phase of the breathing cycle. 4D-PET data were acquired in the gated mode, where each breathing cycle was divided into ten 0.5 s bins. For both CT and PET acquisitions, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to respiratory phase. The effect of 4D acquisition on improving the co-registration of PET and CT images, reducing motion smearing, and consequently increase the quantitation of the SUV, were investigated. Also, quantitation of the tumor motions in PET, and CT, were studied and compared. 4D-PET with matching phase 4D-CTAC showed an improved accuracy in PET-CT image co-registration of up to 41%, compared to measurements from 4D-PET with clinical-CTAC. Gating PET data in correlation with respiratory motion reduced motion-induced smearing, thereby decreasing the observed tumor volume, by as much as 43%. 4D-PET lesions volumes showed a maximum deviation of 19% between clinical CT and phase- matched 4D-CT attenuation corrected PET images. In CT, 4D acquisition resulted in increasing the tumor volume in two patients by up to 79%, and decreasing it in the other two by up to 35%. Consequently, these corrections have yielded an increase in the measured SUV by up to 16% over the clinical measured SUV, and 36% over SUV's measured in 4D-PET with clinical-CT Attenuation Correction (CTAC) SUV's. Quantitation of the maximum tumor motion amplitude, using 4D-PET and 4D-CT, showed up to 30% discrepancy between the two modalities. We have shown that 4D PET/CT is clinically a feasible method, to correct for respiratory motion artifacts in PET/CT imaging of the thorax. 4D PET/CT acquisition can reduce smearing, improve the accuracy in PET-CT co-registration, and increase the measured SUV. This should result in an improved tumor assessment for patients with lung malignancies.

Respiration-correlated spiral CT: a method of measuring respiratory-induced anatomic motion for radiation treatment planning.

We describe a method for generating CT images at multiple respiratory phases with a single spiral CT scan, referred to as respiratory-correlated spiral CT (RCCT). RCCT relies on a respiration wave form supplied by an external patient monitor. During acquisition this wave form is recorded along with the initiation time of the CT scan, so as to "time stamp" each reconstructed slice with the phase of the respiratory cycle. By selecting the appropriate slices, a full CT image set is generated at several phases, typically 7-11 per cycle. The CT parameters are chosen to optimize the temporal resolution while minimizing the spatial gap between slices at successive respiratory cycles. Using a pitch of 0.5, a gantry rotation period of 1.5 s, and a 180 degrees reconstruction algorithm results in approximately 5 mm slice spacing at a given phase for typical respiration periods, and a respiratory motion within each slice that is acceptably small, particularly near end expiration or end inspiration where gated radiotherapy is to occur. We have performed validation measurements on a phantom with a moving sphere designed to simulate respiration-induced tumor motion. RCCT scans of the phantom at respiratory periods of 4, 5, and 6 s show good agreement of the sphere's motion with that observed under fluoroscopic imaging. The positional deviations in the sphere's centroid between RCCT and fluoroscopy are 1.1+/-0.9 mm in the transaxial direction (average over all scans at all phases +/-1 s.d.) and 1.2+/-1.0 mm in the longitudinal direction. Reconstructed volumes match those expected on the basis of stationary-phantom scans to within 5% in all cases. The surface distortions of the reconstructed sphere, as quantified by deviations from a mathematical reference sphere, are similar to those from a stationary phantom scan and are correlated with the speed of the phantom. A RCCT scan of the phantom undergoing irregular motion, demonstrates that successful reconstruction can be achieved even with irregular respiration. Limitations from x-ray tube heating in our current CT unit restrict the length of the scan region to 9 cm for the RCCT settings used, though this will not be a limitation for a multislice scanner. RCCT offers an alternative to the current method of respiration-triggered axial scans. Multiple phases of respiration are imaged with RCCT in approximately the same scanning time required to image a single phase with a triggered axial scan. RCCT scans can be used in connection with respiratory-gated treatment to identify the patient-specific phase of minimum tumor motion, determine residual tumor motion within the gate interval, and compare treatment plans at different phases.