Quantitative discrimination between oil and water in drilled bore cores via Fast-Neutron Resonance Transmission Radiography.

A novel method utilizing the Fast Neutron Resonance Transmission Radiography is proposed for non-destructive, quantitative determination of the weight percentages of oil and water in cores taken from subterranean or underwater geological formations. The ability of the method to distinguish water from oil stems from the unambiguously-specific energy dependence of the neutron cross-sections for the principal elemental constituents. Monte-Carlo simulations and initial results of experimental investigations indicate that the technique may provide a rapid, accurate and non-destructive method for quantitative evaluation of core fluids in thick intact cores, including those of tight shales for which the use of conventional core analytical approaches appears to be questionable.

New prospective for non-invasive detection, grading, size evaluation, and tumor location of prostate cancer.

BACKGROUND: PSA blood test and other present screening tools fail to provide the required sensitivity and specificity and, at early stages, lack correlation with tumor grade, volume, and location. Thus alternative approaches are highly desired. We present and assess a novel method for PCa detection, grading, volume evaluation and tumor location, based on non-invasive zinc concentration mapping in the gland by means of a dedicated rectal probe. METHODS: Zinc-concentration values measured in histologically examined tissue fragments from needle biopsy of 598 patients were analyzed. They were used to generate computer simulated zinc-concentration maps, further analyzed with image-processing tools. The tumor detection performances versus Gleason grade were assessed. RESULTS: A significant increase of zinc depletion with increasing Gleason pattern (grade) classification was established. Tumor detection performance in zinc-concentration maps progressively improves with the cancer's first component score. Reliable information on the location, size and Gleason-grade combination of the lesion can be extracted for clinically relevant volumes. CONCLUSIONS: Zinc depletion in the prostate peripheral zone is the basis for a novel, non-invasive PCa detection, localization, volume evaluation and grading method. Its realization and application as a pre-biopsy and pre-treatment examination, or a follow-up tool, relies on the development of a dedicated transrectal probe. It should have significant impact on biopsy effectiveness, point at a possible extraprostatic extension and provide critical data for focal treatment. The information on tumor grade and distribution may have an important impact on disease management.

Evaluating the cancer detection and grading potential of prostatic-zinc imaging: a simulation study.

The present work deals with the analysis of prostatic-zinc-concentration images. The goal is to evaluate potential clinically relevant information that can be extracted from such images. In the absence of experimental images, synthetic ones are produced from clinically measured zinc-concentration distributions in certified benign and cancerous tissue samples, classified by the lesion grade. We describe the method for producing the images and model the effect of counting statistics noise. We present in detail the image analysis, which is based on a combination of standard image processing and segmentation tools, optimized for this particular application. The information on lowest zinc value obtained from the image analysis is translated to clinical data such as tumour presence, location, size and grade. Their confidence is evaluated with the help of standard statistical tools such as receiver operating characteristic analysis. The present work predicts a potential for detecting small prostate-cancer lesions, of grade (4+3) and above, with very good specificity and sensitivity. The present analysis further provides data on the pixel size and image counting statistics requested from the trans-rectal probe that will record in vivo prostatic-zinc maps in patients.

Clinical assessment of the cancer diagnostic value of prostatic zinc: a comprehensive needle-biopsy study.

BACKGROUND: The correlation between Zinc concentration in the prostate's peripheral zone to the onset or presence of malignant process needs to be evaluated in detail. METHODS: Zinc concentration was measured in approximately 1-4 mm3 segments of fresh needle-biopsy cores, with X-ray fluorescence, and correlated with the histological findings of these tissue segments. RESULTS: Local Zinc concentration is correlated with the presence of cancer (PCa); the higher the Gleason score the greater the Local Zinc depletion. The Zinc value averaged over the entire extracted tissue is specific only to Gleason score 8-9 PCa. The results refer to patients avoiding Zinc-rich supplements since those show elevated prostatic Zinc concentration in identified cancer tissue. A computer simulation analysis of randomly located 0.03-3.3 cm3 lesions, with particular Gleason score and the measured Local Zinc concentration, revealed a potential diagnostic approach definitely superior to PSA, with sensitivity to the tumor grade and with excellent detection capability for Gleason score >6. Further clinical studies have been designed, both on full prostates after radical prostatectomy as well as on biopsy cores at higher resolution, to establish the accuracy of the method for Gleason score = 6. CONCLUSIONS: The PCa diagnostic potential of Local Zinc concentration is confirmed and there is indication that the amount of Zinc depletion could be used as a measure of the Gleason score of the tumor. Local Zinc concentration mapping has the potential to improve patient selection for biopsy, biopsy site selection and local therapy (e.g., Cryotherapy, Brachytherapy) site selection.

Prostatic Zn determination for prostate cancer diagnosis.

We present our studies of prostatic Zn concentration measurements, carried out in the light of a novel prostate cancer (CAP) diagnosis method proposed by us. The method is based on in vivo prostatic Zn mapping by XRF trans-rectal probe. We report on the extensive clinical studies, intended to assess the validity of the novel proposed diagnostic method. Zn content was measured in vitro in needle-biopsy samples from several hundreds of patients, and was correlated with histological findings and other patient parameters. For this purpose, a technique of absolute Zn content determination in approximately 1mm(3) fresh tissue samples by XRF was developed. The experimental details and the main clinical-evaluation results are presented. We further outline the suggested design of the XRF trans-rectal probe for an efficient in vivo detection and mapping of the Zn fluorescence radiation from the prostate through the rectal wall. Laboratory phantom studies, a preliminary design concept and its expected performance are also reported.

In vivo determination of prostatic zinc: phantom feasibility study.

This paper describes a phantom-based feasibility study for a potential in vivo determination of zinc in prostate, which could bring about improved diagnosis of prostate cancer. An x-ray fluorescence topographic technique was developed, which will permit determination of the Zn content in the prostate through the rectum, namely behind a 2-3 mm thick layer of the rectal wall. The topographic approach, together with a reconstruction method developed here, minimizes the interference of Zn from non-prostatic tissue. The phantom studies show that it will be possible to determine Zn in a prostatic compartment behind a few mm thick layer of tissue using a specially designed transrectal probe. Such a probe is currently under development in our laboratories.

Prostatic zinc and prostate specific antigen: an experimental evaluation of their combined diagnostic value.

PURPOSE: In cancer affected prostate cells lose the ability to concentrate zinc, resulting in a substantial decrease in Zn in the prostate. We investigated the possibility of using prostatic zinc combined with prostate specific antigen (PSA) as a novel tool for the reliable diagnosis of prostate cancer. MATERIALS AND METHODS: Using the x-ray fluorescence method the Zn concentration was determined in vitro in prostate samples extracted by surgery from 28 patients. Clinical records included age, serum PSA, sextant prostate needle biopsy, previous medical therapy, surgical procedure and histological findings. RESULTS: A new relationship was found between Zn in prostate tissue and PSA in blood, which allows improved separation between prostate cancer and benign prostate hyperplasia, and might have a significant impact on the reliable diagnosis of prostate cancer. CONCLUSIONS: Zn concentration is not uniform even in the same anatomical region of the prostate, so that a number of measurements at various locations are required for a diagnostic procedure. The most interesting finding in this study is the relationship between Zn concentration and PSA. A combination of these parameters represents a significant improvement on the diagnostic value of each of them separately and provides a powerful tool for more accurate diagnosis. Although the method may be applied in vitro on biopsy samples, our study underlines the importance of developing a facility for in vivo Zn determination in the prostate.

Gamma resonance absorption. New approach in human body composition studies.

The main stream of body elemental analysis is based on the delayed, prompt, and inelastic neutron interactions with the main elements found in the human body, and subsequent analysis of the measured delayed or prompt gamma ray spectra. This methodology traditionally was, and still is, applied for whole body analysis and requires relatively high radiation doses. A new method, based on gamma nuclear resonance absorption (GNRA), is being established at Brookhaven National Laboratory as part of its body composition program. The method is element specific with a high tomographic spatial-resolution capability, at a small fraction of the radiation dose used in the current system. The new system, with its components and capabilities, is described below.

Gamma ray nuclear resonance absorption: an alternative method for in vivo body composition studies.

We have evaluated gamma ray nuclear resonance absorption (gamma-NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the gamma-NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. gamma-NRA is a full imaging technique that essentially constitutes element-specific absorptiometry--i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of gamma-NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) gamma-NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body.

Improvement of the prompt-gamma neutron activation facility at Brookhaven National Laboratory.

The prompt-gamma neutron activation facility at Brookhaven National Laboratory was upgraded to improve both the precision and accuracy of its in vivo determinations of total body nitrogen. The upgrade, guided by Monte Carlo simulations, involved elongating and modifying the source collimator and its shielding, repositioning the system's two NaI(Tl) detectors, and improving the neutron and gamma shielding of these detectors. The new source collimator has a graphite reflector around the 238PuBe neutron source to enhance the low-energy region of the neutron spectrum incident on the patient. The gamma detectors have been relocated from positions close to the upward-emerging collimated neutron beam to positions close to and at the sides of the patient. These modifications substantially reduced spurious counts resulting from the capture of small-angle scattered neutrons in the NaI detectors. The pile-up background under the 10.8 MeV 14N(n, gamma)15N spectral peak has been reduced so that the nitrogen peak-to-background ratio has been increased by a factor of 2.8. The resulting reduction in the coefficient of variation of the total body nitrogen measurements from 3% to 2.2% has improved the statistical significance of the results possible for any given number of patient measurements. The new system also has a more uniform composite sensitivity.

A proposed method for in vivo determination of lithium in human brain.

A method for measuring Li in vivo in human brain is presented. The technique is based on the measurement of tritium gas exhaled by the subject following neutron irradiation of the organ of interest. The gas collection facility used to separate minute amounts of tritium from the breath is described. Methods for reducing the background levels of tritium were investigated. The limit of detection of the system is estimated to be 350 micrograms of Li for the whole brain for a dose of 10 mSv. This detection limit is sufficient for the study of patients treated with lithium compounds, but is too high to study 'normal' brain lithium content. The rate of elimination of tritium gas from the body was also investigated in animal studies. The method also appears suitable for the measurement of lithium levels in the kidney.

Whole body cellular and collagen nitrogen in healthy and wasted man.

The classical literature shows that wasting of body protein takes place mainly from the cellular compartment leaving high proportions of extracellular collagen. Whole body nitrogen ( WBN ) is proportional to whole body protein (cellular + extracellular) while whole body potassium ( WBK ) is almost entirely intracellular. WBK might be an adequate index of cellular wasting. WBN was measured by neutron activation and WBK by counting 40K in 29 healthy males and 131 male and female patients with wide ranges of body composition. Our wasted patients with Crohn's disease or ulcerative colitis, had higher WBN / WBK ratios than matched healthy controls and the difference between the two groups was in the cellular ratio (23.6 mol of N/mol of K, 0.33 g of N/mmol of K, 3 mmol of K/g of N). A multiple regression model for all the subjects represented cellular nitrogen by a term in WBK and extracellular nitrogen by simple anthropometric measurements. The partial regression coefficient of WBN on WBK was 22.6 +/- 1.1 (SE) mol of N/mol of K; this was also similar to the cellular ratio. Our results were compatible with extracellular protein (mainly collagen, which is 35% of normal whole body protein) remaining resistant to wasting even when severe loss of cellular protein occurs. The high ratios of WBN / WBK in wasted patients can be explained by this disproportionate wasting of cellular substances and they do not imply alterations in the cellular N/K ratio. We suggested that the stable ratio of WBK to cellular protein makes it an effective index of cellular wasting. The resistance of collagen to wasting and the preponderance of extracellular mass in the fat-free mass of wasted subjects, make WBN and fat-free mass unreliable guides to the extent of wasting.

An improved calibration for the in vivo determination of body nitrogen, hydrogen, and fat.

Additional investigation of the authors' original technique for measuring total body nitrogen by prompt gamma neutron activation has demonstrated the need for certain changes in the calibration procedures in order to apply the method to studies of patients with abnormal metabolism. In the present technique, total body nitrogen, hydrogen, and fat were derived, simultaneously, from data obtained by neutron capture gamma-ray analysis combined with the measurements of body weight, total body water, and total body calcium. In this improved calibration technique total body nitrogen is more accurately measured, not only in normal subjects, but also in obese subjects and in patients with marked changes in hydration, such as cancer patients. The fat values calculated do not rely on a fixed relationship of total body water or total body potassium with lean body mass as in the previous studies, but are calculated as the difference between body weight and the sum of body water, protein and bone mineral ash. This improved technique has been applied to the study of three groups of subjects, the general population with a normal weight distribution and two extremes represented by obese and cancer patients.

Evaluation of body composition and nitrogen content of renal patients on chronic dialysis as determined by total body neutron activation.

Total body protein (nitrogen), body cell mass (potassium), fat, and water were measured in 15 renal patients on maintenance hemodialysis (MHD). Total body nitrogen was measured by means of prompt gamma neutron activation analysis; total body water was determined with tritium labeled water; total body potassium was measured by whole body counting. The extracellular water was determined by a technique utilizing the measurement of total body chloride and plasma chloride. When compared with corresponding values of a control group of the same age, sex, and height, the protein content, body cell mass, and total body fat of the MHD patients were within the normal range. The only significant change was an increase in the extracellular water/body cell mass ratio in the male MHD patients compared to the controls. The lack of significant difference of the nitrogen values of the MHD patients compared to matched controls suggests that dialysis minimizes any residual effects of uremic toxicity or protein-calorie malnutrition. These findings further suggest that there is a need to reevaluate the traditional anthropometric and biochemical standards of nutritional status for MHD patients. It was concluded that it is particularly important to measure protein stores of MHD patients with low protein intake to ascertain nutritional status. Finally, in vivo measurement of total body nitrogen and potassium for determination of body composition provides a simple, direct, and accurate assessment of the nutritional status of MHD patients.

Indexes of body cell mass: nitrogen versus potassium.

In vivo neutron activation has provided investigators with a powerful tool for research on body composition. Total-body nitrogen (TBN), total-body potassium (TBK), and total-body water (TBW) were measured in 133 normal subjects. TBN, measured by neutron activation, is a measure of total-body protein, an index of body cell mass. TBK, also measured by a nuclear reaction, is an index of body cell mass as well as lean body mass. The mass and protein content of two compartments, muscle and nonmuscle lean tissue, were determined from the combined TBN-TBK data by compartmental analysis. In this study, nitrogen was separated into the actively metabolizing body cell mass component and the slowly metabolizing structural component. The TBK, which is 95% intracellular, was found to be more closely related to the actively metabolizing nitrogen than to TBN. The relationship of body cell mass, a concept originally proposed by Moore, to lean body mass, is shown through the relationship of TBN and TBK. The clinical significance of this study, is that TBK is the more sensitive and reliable indicator of changes in body cell mass. Maximum information on body composition, however, is obtained by the measurement of both TBK and TBN.

Feasibility of noninvasive analysis of lead in the human tibia by soft x-ray fluorescence.

A postmortem study was conducted to assess the feasibility of measuring bone lead concentrations noninvasively in vivo. Characteristic L x rays were induced with an external source of 125I in the superficial tibial cortex of the intact legs of six adults who had no history of occupational exposure to lead. Tibial lead concentrations in the same bones subsequently determined by flameless atomic absorption spectroscopy varied from 15 to 35 micrograms Pb/g wet weight. The upper limit for the modern normal range of lead in the bone is about 25 mg Pb/g wet tissue. The linear correlation coefficient (r) between the measurements made with x-ray fluorescence and lead concentration by absorption spectroscopy was 0.90. Radiation doses of 10 mGy (1 rad) to 1 cm2 of skin, with associated doses to the marrow of adjacent bone of about 0.6 mGy (60 mrad), yielded net lead fluorescence signals ranging from one to seven times the standard deviation of background.

Effects of caloric restriction on body composition and total body nitrogen as measured by neutron activation.

The purpose of this study was to compare the effects of two isocaloric diets (800 Kcals) on the changes in body composition during weight reduction. While the protein content of both diets was 70 g, the carbohydrate content of diet A was 10 g and that of diet B was 70 g. The various parameters of body composition were determined as follows: Total body potassium (TBK) by 40K counting, total body water (TBW) by the tritiated water technique, total body nitrogen (TBN) by prompt gamma neutron activation analysis (PGNAA) and total body fat was estimated by measuring the skinfold thickness. Routine serum chemistries were performed every 2 wk and serum insulin and triiodothyronine by radioimmunoassay were done at 4-wk intervals. Seventeen obese women who were at least 30% above ideal body weight volunteered for the outpatient study, (group A--10 subjects, group B--7 subjects). At the end of the 12 wk study, the percent changes in the above parameters of body composition were not significantly different for the two groups. The biochemical changes were consistent with the degree of caloric restriction. We conclude that: (1) the technique of prompt gamma neutron activation analysis can be used effectively to determine long term changes in total body nitrogen during weight reduction, (2) loss of lean tissue (water, potassium and nitrogen) as well as fat tissue occurred during weight reduction. The loss of TBN in absolute quantities was less for diet A compared to diet B; however, there was no significant difference between the two diets when the data was expressed as a percent change from the baseline values, and (3) TBK determination probably provides the best estimate of total body fat.