Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same...

15
IN VIVO NEUTRON ACTIVATION FACILITY AT BROOKHAVEN NATIONAL LABORATORY Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., and F. Avraham Dilmanian, Ph.D. Medical Dept., Brookhaven National Laboratory, Upton, NY 11973 ABSTRACT Seven important body elements, C, N, Ca, P, K, Na, and C1, can be measured with great precision and accuracy in the in vivo neutron activation facilities at Brookhaven National Laboratory. The facilities include the delayed-gamma neutron activation, the prompt-gamma neutron activation, and the inelastic neutron scattering systems. In conjunction with measurements of total body water by the tritiated-water dilution method several body compartments can be defined from the contents of these elements, also with high precision. In particular, body fat mass is derived from total body carbon together with total body calcium and nitrogen; body protein mass is derived from total body nitrogen; extracellular fluid volume is derived from total body sodium and chlorine; lean body mass and body cell mass are derived from total body potassium; and, skeletal mass is derived from total body calcium. Thus, we suggest that neutron activation analysis may be valuable for calibrating some of the instruments routinely used in clinical studies of body composition. The instruments that would benefit from absolute calibration against neutron activation analysis are bioelectric impedance analysis, infrared interactance, transmission ultrasound, and dual energy x-ray/ photon absorptiometry.

Transcript of Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same...

Page 1: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

IN VIVO NEUTRON ACTIVATION FACILITY AT BROOKHAVEN NATIONAL LABORATORY

Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., and F. Avraham Dilmanian, Ph.D.

Medical Dept., Brookhaven National Laboratory, Upton, NY 11973

ABSTRACT

Seven important body elements, C, N, Ca, P, K, Na, and C1, can be

measured with great precision and accuracy in the i n vivo neutron

activation facilities at Brookhaven National Laboratory. The

facilities include the delayed-gamma neutron activation, the

prompt-gamma neutron activation, and the inelastic neutron

scattering systems. In conjunction with measurements of total

body water by the tritiated-water dilution method several body

compartments can be defined from the contents of these elements,

also with high precision. In particular, body fat mass is derived

from total body carbon together with total body calcium and

nitrogen; body protein mass is derived from total body nitrogen;

extracellular fluid volume is derived from total body sodium and

chlorine; lean body mass and body cell mass are derived from

total body potassium; and, skeletal mass is derived from total

body calcium. Thus, we suggest that neutron activation analysis

may be valuable for calibrating some of the instruments routinely

used in clinical studies of body composition. The instruments

that would benefit from absolute calibration against neutron

activation analysis are bioelectric impedance analysis, infrared

interactance, transmission ultrasound, and dual energy x-ray/

photon absorptiometry.

Page 2: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

2

I. INTRODUCTION

Measurements of in vivo body composition are vital to research in

growth and development’, the aging process’, malnutrition’, and

diseases, such as osteo~~orosis4 and the acquired immunodeficiency

syndrome (AIDS)’ . The current widespread interest in the study of body composition indicates the importance of having a rapid,

reliable, and relatively inexpensive way af determining it.

However, most instruments used in clinical. research have not been

calibrated against absolute standards.

The in vivo neutron acti.vation (IVNA) faci.lities at Brookhaven

National Laboratory (BNI,) have been used to measure body

composition f o r such researches for more than 20 yearsc-”. With

our experience in designing and making phantoms, Monte Carlo

simulation, and in.model.ing body composition, we can readily and

accurately calibrate other instruments against IVNA.

11. NEUTRON ACTIVATION FACILITIES AT BNL

A. The delayed-gamma neutron activation (DGNA) facility

The DGNA system consists of a whole body c:ounter (WBC) and a

whole-body neutron activation system that uses ‘38P~Be neutron

sources. The WBC consists of a special counter room containing 32

Page 3: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

DISCLAIMER

This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, make any warranty, express or implied, or assumes any legal liabili- ty or responsibility for the accuracy, completeness, or usefulness of any information, appa- ratus, product, or process disclosed, or r e p e n t s that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessar- ily state or reflect those of the United States Government or any agency thereof.

Page 4: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since
Page 5: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

3

NaI(T1) crystals that provide high sensitivity and high

resolution for detecting radionuclides. Each of the 32 crystals

is 4" (W) x 4'' (H) x 18'' (L) with 16 detectors above and 16 below

the patient's bed. The entire room is shielded by four feet of

low-radioactivity concrete, and a 4-in steel, 1/8-in lead and

1/16-in aluminum liner. The absolute photopeak efficiency of the

WBC is about 20% for a uniform line source of I 3 l I (364.5 keV)

placed axially on the bed. This arrangement gives a statistical

fluctuation of 1.7% in y-ray counts for a 10-minute measurement

of a 1 nCi I3 'I line source. The detection limit of WBC is

approximately 1 nCi of radioactivity in the body.

The WBC is used to measure total body potassium (TBK) by counting

the radioactive isotope 40K. An anthropomorphic hollow phantom,

filled with a solution containing a known amount of K, is used to

calibrate the WBC for TBK measurements. Recently, we upgraded the

WBC data acquisition system to provide faster and easier

collection, storage, display, and analysis of data''.

To investigate the total body content of other elements, such as

Ca, Na, C1, and P, the person is activated in the whole-body

neutron activation facility, then counted in the WBC. The

measurements of total body calcium in the DGNA facility

originally were calibrated with an anthropomorphic hollow phantom

filled with solutions containing predetermined amounts of Ca6.

However, 99% of the total Ca in the human body is contained

Page 6: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

4

within the skeleton and is not homogeneously distributed.

Recently, an artificial skeleton was designed, constructed, and

placed in a bottle mannequin absorber pharntom12 to better

represent this distribution; now, the DGNA system is calibrated

with this phantom containing the artificial This

change has improved the accuracy of the measurements. Also, the

simple geometry of this phantom and the artificial skeleton

allows us to simulate thie neutron activation process using a

Monte Carlo code, so ena.bling us to calibrate the system for

people larger and smaller than the phantoms used as standards.

B. The prompt-gamma neutron activation (PGNA) facility

The PGNA system has undergone several upgrading since it was

built in the late 1970~;~” in particular the system underwent

extensive upgrading in 1991 to improve its reliability and the

precision of the measurements of total body nitrogen (TBN)”.

The facility uses a 75.5, Ci “‘PuBe neutron source positioned

under the patient’s bed, and two 15.2 cm x’ 15.2 cm NaI(T1)

detectors positioned close to the patient’s sides. Measurements

are taken, with the pers’on in both the supine and prone

positions. At each position, the patient’s bed passes over the

source along the direction of the body axis in a step-and-shoot

method, in which measurements are recorded. at five of 20-cm steps

of 200 s each. A 2.5 cm-high tank of D 2 0 positioned immediately

Page 7: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

5

underneath the patient's bed acts as a premoderator, increasing

the amount of epithermal neutrons at the entrance to the

patient's body. The system uses total body hydrogen (TBH) as an

internal standard', i.e. it measures the ratio of counts from the

10.8 MeV y line of I4N neutron capture events to the counts from

the 2.23 MeV y emission of the 'H neutron capture reaction. The

TBH assessment includes measurements of total body water and

body-composition modeling.

The PGNA system is calibrated with three bottle mannequin

absorber phantoms1* of different sizes15 filled with same

solution. We found that the ratio of the nitrogen to hydrogen

counts can be approximated by a linear function of phantom

volume. Corrections for body size thus were derived, and used for

TBN measurements of people of different sizes.

C. The inelastic scattering (INS) facility

Because of the high carbon content in fat and because a high

fraction of TBC is in the body fat, the INS method is considered

the most direct way to measure total body fat. The INS system at

BNL uses a pulsed D-T Zetatron generator to produce 14 MeV

neutrons at a 10 kHz repetition rate. The 4.4 MeV y-rays emitted

from the patient are detected in two 15.2 cm x 15.2 cm

NaI(T1) detectors positioned on both sides of the person. A

plastic scintillator is used to count the total number of

Page 8: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

6

neutrons produced by the! generator during the measurements.

Patients are measured from the shoulder to the knee in both

supine and prone positions on a bed that traverses the neutron

source. Data collection and the motion of the bed are controlled

by a computer.

The INS system is calibrated with an anthropomorphic hollow

phantom filled with a solution with predetermined amount of Cll.

DO Summary of the precisions and doses f o r elemental

measurements at BNL:

Table 1. summarizes the precisions and radiation doses fo r

elemental measurements performed at BNL. The precision of the

elemental measurements is estimated based on repeated

measurements with human subjects (TBK) and with phantoms

containing the amount of the element of interest close to that in

Reference ManI6. The radiation doses are estimated for a typical

measurement in each of the three facilities using a quality

factor of 20 for neutrons.

111. CALIBRATION OF BOD'Y COMPOSITION MEASUREMENTS

Although all of the devices used for routine clinical

measurements of body composition are calibrated against standards

Page 9: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

7

provided by the manufacturers, few, if any, of them are based on

absolute elemental composition, and for many of these techniques,

human measurements are the only proper method of evaluating the

system performance. Furthermore, although the precision of most

instruments is quite good when measuring the standard, the

accuracy of some of them is subject to errors. These errors may

be in part, due to inadequate corrections for differences in body

size and shape. Also, instruments from the same manufacturer when

measuring the same compartment at different sites yield results

that are statistically different.

Since IVNA is based on direct elemental measurements, body

elemental composition can be determined with high precision and

accuracy. Thus, IVNA can be used as the standard to calibrate

body composition instruments now widely used in clinical

settings. In fact, the BNL IVNA facilities have already been used

for several inter-method calibrations, mostly with the dual

photon x-ray absorptiometry

ACKNOWLEDGMENTS

This research was supported by the Department of Energy under

contract DE-AC02-76CH00016, and by the National Institutes of

Health grant 1-Pol-DK42618.

Page 10: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

8

REFERENCES:

1. Fomon, S.J., Haschk:e, F., Ziegler, E.E. and Nelson, S.E.

Body composition of reference children from birth to age 10

years Am J Clin Nutr, 1982 35: 1169

2. Cohn, S.H., Vaswani., A.N., Zanzi, I. and Ellis, K.J.

Effects of aging OCI bone mass in adult women, Am J Physiol,

1976 230: 143-148

3. Barac-Niet, M., Spurr, G.B., Lotero, G.B., Maksud, M.G.,

Dahners, H.W., Body composition during nutritional repletion

of severely undernourished men Am J Clin Nutr, 1979, 32:

98 1-9 9 1

4. Aloia, J . F . , Vaswani, A . N . , Yeh, J.K., Ross, P.L., Flaster,

E., and Dilmanian, F.A., Calcium supplementation with and

without hormone replacement therapy to prevent

postmenopausal bone loss, Ann Int Med, 1994 120 (2) 97-103

5. Kotler, D.P., Tierney, A.R., Altilio, D., Wang, J., and

Pierson, R.N.,Jr., The magnitude of body cell mass depletion

determines the timing of death from wasting in AIDS, Am J

Clin Nutr, 1989 444-447 (1989)

Page 11: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

9

6 . Cohn, S.H., Shukle, K.K., Dombrowski, C.S., and Fairchild,

R . G . , Design and calibration of a tlbroad-beamlf 238P~Be

neutron source for total body neutron activation analysis, J

Nucl Med 1972 13: 487-492

7. Vartsky, D., Ellis, K.J., and Cohn, S.H., In vivo

measurement of body nitrogen by analysis of prompt gammas

from neutron capture, J Nucl Med 1979 20: 1158

8 . Vartsky, D., Pretswich, W.V., Thonmas, B.J., Dabek, J.T.,

Chettle, D.R., Fremlin, J.H., and Stammers, K., The use of

body hydrogen as an internal standard in the measurement of

nitrogen in vivo by prompt neutron capture gamma ray

analysis J Radioanal Chem 1979 48: 243-52

9. Kehayias, J.J., Ellis, K.J., Cohn, S.H., and Weinlein, J.H.,

Use of a high repetition rate generator f o r in vivo body

composition measurements via neutron inelastic scattering,

Nucl Instr and Meth 1987 B24/25, 1006:1009,

10. Dilmanian, F.A., Weber, D.A., Yasumura, S., Kamen, Y.,

Lidofsky, L., Heymesfield, S . B . , Pierson, R.N., Jr., Wang,

J., Kehayias, J. and Ellis, K.J., Performance of the neutron

activation systems at Brookhaven National Laboratory, in

Advances in In Vivo Body Composition Studies, Yasumura, S.,

Harrison, J.E., McNeil, K.G., Woodhead, A . D . , and

Page 12: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

i

10

Dilmanian, F.A., ed., 1990 Plenum Press, New York,

la. Ma, R., Dilmanian, F.A., Rarback, H.M., Stamatelatos, I.,

Meron, M., Kamen, Y., Yasumura, S., Weber, D.A., Lidofsky,

L.J., and Pierson, Jr., R.N. Recent upgrade of the IVNA

facility at Brookhaven National Laboratory, in Proceedings

of the International Symposium on In Vivo Body Composition

Studies, Houston, TX, 1992

12. Bush, F., Energy absorption in radium therapy, Br. J.

Radiol. 19, 14-21 1946

13. Ma, R,, Zhao, X., Rarback, H.M., Yasumura, S., Dilmanian,

F . A . , Moore, R.I., Lo Monte, A.F., Vodopia, K.A., Liu, H.B. , Economos, C.D., Nelson, M.E., Aloia, J.F., Vaswani, A.N.,

Weber, D.A., Pierson, R.N. Jr., and Joel, D.D.,

Calibration of the delayed-gamma neutron activation

facility, Med Phys 1996 23 (2), p273-277

14. Yasumura, S. Ma, R., Weber, D.A., Dilmanian, F.A., Zhao, M.,

Lomonte, A.F., Moore, R . I . , Skelany, R., and Pierson, R.N.,

Jr., A modified bottle mannequin (BO.MAB) phantom for in

vivo neutron activation analysis, Health Physics (in press)

15. Dilmanian, F.A., Lidofsky, L.J., Stamatelatos, I., Kamen,

Y., Yasumura, S., Vartsky, D., Pierson, R.N. Jr., Weber,

Page 13: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

t

11

D.A., Moore, R.I. and Ma, R., Improvement of the prompt-

gamma neutron activation facility at Brookhaven National

Laboratory, Submitted for publication to Physics in Medicine

and Biology 1996

16. Stamatelatos, I.E., Dilmanian, F.A., Ma, R., Lidofsky, L.J.,

Weber, D.A., Pierson, R.N. Jr., Kamen, Y., and Yasumura, S.,

Calibration for measuring total body nitrogen with a newly

upgraded prompt gamma neutron activation facility, Phys Med

Biol, 1993 38: 1

17. ICRP Publication 23. Report of the task group on reference

man, Pergamon Press, New York 1975

18. Heymsfield, S.B., Wang, J, Aulet, M., Kehayias, J.J.,

Lichtman, S., Kamen, Y., Dilmanian, F . A . , Lindsey, R., and

Pierson, R.N. Jr., Dual Photon Absorptiometry: Validation

of Mineral and Fat Measurements In: In Vivo Body

Composition Studies: Recent Advances pp 3 2 7 - 3 3 7 Yasumura, S.

Harrison, J.E., McNeill, K.G., Woodhead, A.D. and

Dilmanian, F.A. Editors Basic Life Sciences, Vol 55

Plenum Press, New York 1990

19. Pierson, R.N. Jr., Wang, J., Heymsfield, S . B . , Russel-Aulet,

M., Mazariegos, M., Tierney, M., Smith, R., Thornton, J.,

Kehayias, J., Weber, D.A., Dilmanian, F.A., Measuring Body

Page 14: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

12

Fat: Intermethod Cclmparisons in 388 Normal Caucasian

Subjects J Physiol 261 (Endocrinol Metab 24):E190-E198 1991

Key Words: In vivo neutron activation, body composition, phantom,

calibration

Page 15: Ruimei Ma, Ph.D., Seiichi Yasumura, Ph.D., F. Avraham .../67531/metadc697243/...measuring the same compartment at different sites yield results that are statistically different. Since

Table 1. Summary of precisions and radiation doses for the elemental measurements performed at BNL.

Elements Facility Precision (%) Radiation Dose

K WBC 1.0 ~ 0 . 0 1 (from

(men)

calibration)

) 575 1 Ca DGNA 1 .5

Na DGNA 1 .6

c1 DGNA 1 . 7

P DGNA 2 . 5

N PGNA 2.2 -I

80

C INS 3.0 50