The signature-based radiation-scanning approach to standoff detection of improvised explosive devices.

The signature-based radiation-scanning technique for detection of improvised explosive devices is described. The technique seeks to detect nitrogen-rich chemical explosives present in a target. The technology compares a set of "signatures" obtained from a test target to a collection of "templates", sets of signatures for a target that contain an explosive in a specific configuration. Interrogation of nitrogen-rich fertilizer samples, which serve as surrogates for explosives, is shown experimentally to be able to discriminate samples of 3.8L and larger.

Signature-based radiation scanning using radiation interrogation to detect explosives.

Improvised explosive devices (IEDs) pose a serious threat to society. The signature-based radiation scanning technology has been developed to counter this threat. This technology can be automated, requires minimal operator involvement, and in principle can rapidly identify IEDs from standoff distances. Preliminary research using neutron interrogation indicates that explosive samples of about 7 kg or greater hidden in various targets can be detected from standoff distances of more than a meter, with high sensitivity and high specificity.

Detection of chemical explosives using multiple photon signatures.

A template-matching procedure is being investigated for rapid detection of improvised explosive devices at standoff distances. Photon-scattered and photon-induced positron annihilation radiation responses are being studied as a part of a signature-based radiation scanning approach. Back-streaming radiation responses, called signatures, are compared to templates, which are collections of the same signatures if the interrogated volume contained a significant amount of explosive. Experiments have been conducted that show that explosive surrogates (fertilizers) can be distinguished from several inert materials.

On X-ray back-scattering to detect hidden cracks in multi-layer structures.

A method that uses X-ray scanning to detect subsurface cracks is described. The method deals with samples typical of aircraft structures for which access is limited to one surface and a crack is hidden within the first substrate layer beneath the surface layer. A single-scatter model for the total response due to all X-rays that scatter once in one of the substrate layers and then pass through the top surface of the crack region and escape the target is developed. In this model, the crack is treated as a region of lower average density, and hence interaction coefficient, than the unaffected bulk material. The EGS4 Monte Carlo code also is used to estimate multiple-scattering response assuming the crack region is a thin void. These two models provide consistent results which indicate that properly designed X-ray back-scatter scanners can identify the presence of hidden cracks that extend through the substrate layer and are greater than about 1 cm in length.

Flaw detection by X-ray scanning using the rolling-window template-matching procedure.

An X-ray scanning method to nondestructively detect flaws that are hidden from direct observation is demonstrated. The method employs a rolling-window template-matching procedure that identifies statistically significant deviations between a response matrix characteristic of an unflawed sample and a response matrix obtained from a test sample. The methodology is illustrated with simulated data and implemented to measure the thickness of missing material hidden within engineered samples. The technology has application in detecting flaws in systems such as aircraft.

Biodistribution and dosimetry of [(18)F]fluorodeoxyglucose labelled leukocytes in normal human subjects.

SUMMARY: This study was performed in order to assess [(18)F]fluorodeoxyglucose white blood cell ((18)F-FDG WBC) dosimetry in normal human subjects. Using previously reported methods, mixed cell suspensions of autologous leukocytes were prepared from four normal volunteers. Leukocytes were labelled in heparin-saline by incubation with (18)F-FDG at 37 degrees C for 20 min. After washing and resuspension, (18)F-FDG WBCs (225-315 MBq) were administered by intravenous injection. Whole-body imaging was performed at 0.5, 1, 2, 4 and 6 h using a GE Varicam with 511 keV collimation. Blood samples were obtained at corresponding times as well as fractionated urinary collection. Whole-body anterior and posterior images were used for calculation of organ dosimetry. Uptake of (18)F-FDG WBCs occurred predominantly within the reticulo-endothelial system. Plasma activity, urinary excretion (9.9+/-2.3% at 6 h), and brain uptake (1.7+/-0.4%) were consistent with partial elution of (18)F-FDG. Positron emission tomography imaging performed at 5-6 h after injection yielded good quality images of reticulo-endothelial uptake. Whole-body and organ dosimetry for (18)F-FDG WBCs in doses of 225-250 MBq are comparable with reported results for conventional doses of (111)In oxine labelled leukocytes. Further studies of (18)F-FDG WBC as an agent for positron emission tomography imaging of inflammatory disease appear warranted.

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma.

Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received (111)In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8 ) on day 0 followed by a therapeutic dose of 90Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of (111)In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T(1/2), blood AUC, plasma T(1/2), and plasma AUC. It is concluded that 90Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T(1/2), reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.

Updated data on proximal femur bone mineral levels of US adults.

This paper describes data on bone mineral levels in the proximal femur of US adults based on the nationally representative sample examined during both phases of the third National Health and Nutrition Examination Survey (NHANES III, 1988-94), and updates data previously presented from phase 1 only. The data were collected from 14,646 men and women aged 20 years and older using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in four selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter and total. These variables are provided separately by age and sex for non-Hispanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). NHW in the southern United States had slightly lower BMD levels than NHW in other US regions, but these differences were not sufficiently large to prevent pooling of the data. The updated data provide valuable reference data on femur bone mineral levels of noninstitutionalized adults. The updated data on BMD for the total femur ROI of NHW have been selected as the reference database for femur standardization efforts by the International Committee on Standards in Bone Measurements.

On the number of automated timed manual performance trials to administer.

OBJECTIVE: To determine the number of trials needed to obtain satisfactory results when evaluating function in older subjects using the automated version of the Williams short (three-door) Timed Manual Performance (TMP) test. DESIGN: Administration of from one to five trials in succession on a given test date. SETTING: A Continuing Care Retirement Community (CCRC), assisted living centers, nursing homes, and a community residence, all located in central North Carolina. PARTICIPANTS: The subject population consisted of 182 older volunteers, aged 63 to 100 years. One hundred nineteen lived independently in a CCRC, 33 were assisted-living residents, 29 lived in nursing homes, and one lived independently in the community. Each subject was administered at least three trials in succession on his or her first test date; 23 of the independently living CCRC residents were given three trials on a second test date. The community-dwelling volunteer was administered from one to five trials on each of 26 test dates over an approximately 16-month period. MEASUREMENTS: The time it takes to perform five door opening and closing operations as measured by the three-door Cognatemp Automated Timed Manual Performance (ATMP) system. MAIN RESULTS: Average ATMP time for the subjects living independently decreased approximately 10% between the first two trials but negligibly between trials two and three. The more dependent groups continued to improve between trials two and three. The community-dwelling subject tended to improve in the first three or four trials and to decline by the fifth trial. CONCLUSIONS: It is recommended that two trials be administered and the best time used; if neither trial results in a time less than 10 seconds, one or two more trials should be administered. It is generally not necessary nor advantageous to administer more than four trials.

Prevalence of low femoral bone density in older U.S. adults from NHANES III.

Most estimates of osteoporosis in older U.S. adults have been based on its occurrence in white women, even though it is known to affect men and minority women. In the present study, we used dual-energy X-ray absorptiometry measurements of femoral bone mineral density (BMD) from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) to estimate the overall scope of the disease in the older U.S. population. Specifically, we estimate prevalences of low femoral BMD in women 50 years and older and explore different approaches for defining low BMD in older men in that age range. Low BMD levels were defined in accordance with an approach proposed by an expert panel of the World Health Organization and used BMD data from 382 non-Hispanic white (NHW) men or 409 NHW women ages 20-29 years from the NHANES III dataset. For women, estimates indicate 13-18%, or 4-6 million, have osteoporosis (i.e., BMD > 2.5 standard deviations [SD] below the mean of young NHW women) and 37-50%, or 13-17 million, have osteopenia (BMD between 1 and 2.5 SD below the mean of young NHW women). For men, these numbers depend on the gender of the reference group used to define cutoff values. When based on male cutoffs, 3-6% (1-2-million) of men have osteoporosis and 28-47% (8-13 million) have osteopenia; when based on female cutoffs, 1-4% (280,000-1 million) have osteoporosis and 15-33% (4-9 million) have osteopenia. Most of the older U.S. adults with low femur BMD are women, but, regardless of which cutoffs are used, the number of men is substantial.

Monte Carlo analysis of multi-layer targets for production of 15O.

A Monte Carlo simulation code was written to analyze multi-layer targets for production of 15O. The code models beam-particle transport through the target and production and transport of generated radionuclides; it can be used to assess the effects on radionuclide production of several beam and target design variables. A pathlength correction feature is included that relaxes restrictions inherent in previous ion transport codes and a variance reduction procedure is implemented that significantly improves code efficiency.

Cold spots on bone scans in patients wearing weighted breast prostheses.

A bone scan is frequently obtained in patients with breast cancer for evaluation of possible metastatic bone disease or for evaluation of response of known metastases to treatment. These patients commonly wear breast prostheses after unilateral or bilateral mastectomies. On some bone scans, the authors have observed artifacts resulting from certain breast prostheses. In particular, in the patient described, a weighted breast prosthesis was not removed during Tc-99m HMDP bone scanning and was interpreted as being permanent pacemaker or defibrillation unit. The scintigraphic appearance of several commonly used, commercially available weighted breast prostheses is discussed.

Technical pitfalls in image acquisition, processing, and display.

Optimal image quality is an ideal in nuclear medicine that is not always realized, being subject to a variety of conditions that can act, either singly or in combination, to undermine its accomplishment. These conditions include potential defects and limitations in both the hardware and software used for the acquisition and reconstruction of nuclear medicine images. Factors relating to individual patients can contribute to these obstacles, including limitations in mobility and compliance. Importantly, suboptimal or erroneous technique is a common source of poor imaging results, with loss of diagnostic efficacy. Appropriate test selection and careful attention to patient preparation and procedural details are essential elements in avoiding image flaws and artifacts in nuclear medicine.

Bone scintigraphy evaluated in diagnosing and staging Langerhans' cell histiocytosis and related disorders.

UNLABELLED: An analysis of patients with proven Langerhans' cell histiocytosis (LCH) was undertaken with the aim of evaluating the role of bone scintigraphy in the diagnosis and staging of LCH. METHODS: Radiographic skeletal surveys and whole-body bone scintigraphy study results were reviewed for all patients treated at the Mayo Clinic in Rochester, Minnesota during 1965-1994 with histologic proven LCH. All available studies were then reported in a randomized and blinded fashion. RESULTS: Of the 73 patients with the histologic diagnosis, 56 (76%) had a definite lesion reported on radiographs and subsequent biopsy-proven bone involvement. For this population, the sensitivity and specificity of radiographic survey were 100% and 61%, respectively, compared to 91% and 55% for bone scintigraphy. Solitary bone lesions were reported on 21 radiographic surveys and 24 bone scintigrams. For solitary lesions, radiograph sensitivity and specificity were 95% and 73%, respectively, compared to 88% and 77% for bone scintigraphy. Bone scintigraphy receiver operating characteristic curves showed the region of greatest diagnostic accuracy to be skull, facial bones and mandible (88% sensitivity, 52% specificity). Radiation dosimetry to adult reproductive organs was less favorable for radiographic skeletal survey compared to bone scintigraphy. CONCLUSION: Our results support the use of radiographic skeletal survey in the initial diagnosis of LCH. Bone scintigraphy may have a role in monitoring a patient's progress in which the initial scintigram and radiographic survey show good correlation.

Filtered technetium-99m-sulfur colloid evaluated for lymphoscintigraphy.

UNLABELLED: Several 99mTc-labeled radiopharmaceuticals have been developed for lymphoscintigraphy of the extremities. In the United States, however, these agents are not widely used clinically. This study evaluates the use of smaller particle sizes ( < 0.1 micron) of 99mTc-sulfur colloid (99mTc-SC) for lymphoscintigraphy. METHODS: The 99mTc-SC was prepared by kit, and the final preparation was filtered through a sterile 0.1-micron filter. The radiochemical purity (RCP) of the filtered 99mTc-SC was determined before administration. Nineteen patients with suspected lymphedema were injected with 18.5 MBq (500 muCi) filtered 99mTc-SC intradermally in each foot, and whole-body images were obtained immediately and 1, 3, 6 and 24 hr later. Local views over the inguinal or axillary lymph nodes were also obtained every 5 min for the first hour. RESULTS: The average RCP value was 93.4% +/- 4.2% (n = 19), and the RCP difference pre- and postfiltration of the 99mTc-SC preparation was -1.7% +/- 1.4% (n = 40). Evaluation of the particle size with the polycarbonate filter showed that 89.9% +/- 4.5% (n = 28) of particles were less than 50 nm, and the particle size was further determined by electron microscopy to be 38.0 +/- 3.3 nm (n = 202). The mean particle sizes of two peaks measured by laser light scattering techniques were 7.5 and 53.9 nm (major peak). Clinical studies with filtered 99mTc-SC demonstrated similar lymphoscintigrams compared with those obtained with 99mTc antimony sulfide colloid (99mTc-ATC). Filtered 99mTc-SC showed a faster transport rate to the inguinal lymph nodes and lower radiation dosimetry for liver, spleen and whole body compared with 99mTc-ATC. CONCLUSION: Filtered 99mTc-SC can be easily prepared and is readily available for routine clinical use in lymphoscintigraphic studies.

Prevalence of low femoral bone density in older U.S. women from NHANES III.

Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34-50% in four different femur regions, which corresponds to approximately 12-17 million women. The prevalence with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17-20%, or approximately 6-7 million women. Prevalences were 1.3-2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000-400,000, respectively; corresponding figures for osteoporosis were 5-6 million, 200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

111In-oxine-labelled granulocyte dosimetry in normal subjects.

The aim of this study was to determine organ uptake and dosimetry in human subjects using 111In granulocytes obtained by ficoll-hypaque purification. Anterior-posterior whole-body imaging was performed at 1, 3, 5, 24 and 48 h after injection of approximately 18.5 MBq (0.5 mCi) 111In granulocytes in 10 normal volunteers. Utilizing relative geometric mean analysis, the fraction of injected activity (FIA) was determined at each imaging time for the kidney, liver, lungs, bone marrow, spleen and whole-body remainder. Residence time was determined by integration of the bi-exponential fit of the FIA data over time. Curve fitting was performed with SAAM software (University of Washington). Red marrow uptake was calculated from activity in the L3-L4 vertebrae and iliac crests. Total body marrow uptake was extrapolated from these data using ICRP 23. Dose was determined with MIRDOSE 2 for the various organs. The liver had the highest organ uptake (40.3% at 48 h). The spleen, liver, red marrow, kidney and lung doses were 4.1, 1.6, 0.8, 0.5 and 0.4 mGy MBq-1, respectively. Urinary and stool excretion was negligible and blood clearance half-time was 6.9 h. Using current methods providing improved quantification of organ uptake and dosimetry, our results confirm the liver, spleen, bone marrow,lungs and kidneys to be the principal target organs of 111In granulocytes.

Proximal femur bone mineral levels of US adults.

This paper describes bone mineral levels in the proximal femur of US adults based on a nationally representative sample of 7116 men and women aged 20 years and older. The data were collected in phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in five selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter, Ward's triangle and total. These variables are provided separately by age and sex for non-HIspanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). BMD and BMC in the five ROI tended to decline with age, whereas area did not. BMD and BMC were highest in NHB, intermediate in MA and lowest in NHW, but areas were highest in NHW, intermediate in NHB and lowest in MA. Men had greater BMD, BMC and area than women in all three race/ethnic groups. Differences by age, sex or race/ethnicity tended to be the largest in Ward's triangle, followed by the femur neck; patterns in the trochanter, intertrochanter and total ROI were reasonably similar to each other. This report provides extensive data on femur bone mineral levels of adults from one of the largest samples available to date and should be valuable as reference data for other studies which examine this skeletal site in adults.

Quality control of bone densitometry in a national health survey (NHANES III) using three mobile examination centers.

A quality control (QC) program for bone mineral measurements at the proximal femur by dual-energy x-ray absorptiometry (DXA) was designed for the osteoporosis component of the Third National Health and Nutrition Examination Survey (NHANES III). Major elements of the QC program are (1) a QC center for review of all scans, (2) setup procedures for and continuous monitoring of daily QC procedures, (3) reference standards for cross-calibration, (4) longitudinal studies for assessment of instrument stability, (5) monitoring of technologist performance, and (6) training. This report describes the results of the QC program of the first half of this 6 year study, which began in 1988. Measurements were performed on 7376 subjects in three mobile examination centers, which traveled to a new location about every 3 months, a total of 44 locations. A small percentage (3.5%) of all scans were rejected, mostly because of patient motion during scanning, but 33% of the remaining scans required reanalysis at the QC center to refine the location of the regions of interest. Precision in spine and hip phantoms was below 1% at all ROIs. In 535 subjects with duplicate scans, age 20-91 of both sexes, examined in a blinded review, precision for BMD at the femur neck ROI was 3.2% (CV) and 5.1% for Ward's triangle BMD. The central review improved scan quality, increased the number of usable scans, and reduced significantly the range of the mean percentage difference in the duplicate scans. Minor alterations in machine function were observed and corrected. QC results on phantoms were similar to those obtained with stationary instruments in dedicated laboratories. Retrospective analysis of the regression slopes from QC records did not show a need for correction of the data base, indicating that the instruments were stable during the course of the study.