Jim Patton and colleagues found an excellent differentiation between  malignant and benign nodules based on thyroid iodine content (TIC) using XRF. Additional utility was obtained when Ge(Li) was used as it also was useful for use with emission scans. The amount of iodine in the gland is an integrated measure of past and present thyroid function, while the emission scan reflects the current functional state of the gland.

Thyroid nodules that contain less iodine than normal tissue (low thyroid iodine content), when coupled with low radioactive iodine uptake in the nodule, provide a strong signature of malignancy. The thyroid studies were done in collaboration with  Endocrine Division faculty (John Hollifield, and Guat Sue Lee).  When the Iodine content in nodules in the first 42 surgically treated patients was lower than 60% that of the contra lateral site they were all found to be malignant (sensitivity 100%, Specificity 79% and overall accuracy 90%). By 1985, the study was extended to include 150 solitary nodule patients with specificity 99%, sensitivity 63%.  A confident judgment of benignancy was when the ratio was > 60%. A 1986 study of 64 hyperthyroid patients showed that I-131 treated patients reached a low TIC nadir at about 3 months. They found that 80% of patients whose TIC fell to <2 mg at 3 months were likely to be hypothyroid within 12 months. If TIC was > 2mg, the chance of hypothyroidism was only about 14%. The frequency of hypothyroidism increases steadily following ¹³¹I therapy, which requires lifetime follow up of ¹³¹I treated patients.

The Brussels VUB group (Jonckheer and Deconinck) published extensive data on TIC in many thyroid states including patients with acute thyroiditis. Patients with acute thyroiditis had rapidly falling TIC, which increased slowly during the recovery phase. This was in accord with our findings in our 2 patients with acute thyroiditis.  Their summary of normal values of thyroid iodine content in different centers shows that results are generally in accord in different  countries, and observed differences reflects mainly geographic differences in iodine content in the diet. Interesting data on variations in thyroid size with iodine in the diet is given in two of their figures.

One other use of XRF system occurred when we were asked to study a patient who a nasal sinus opacity who was suspected to have received thorotrast earlier. The  X-ray fluorescence study confirmed the nature of the material as thorium, based on the characteristic energy of the fluorescent x-rays from the sinus region.

The Vanderbilt XRF system was used routinely until the mid 1980s. Thereafter, when ultrasound and fine needle biopsy came into general use, XRF was replaced for pre surgical nodule evaluation  The few remaining XRF systems still in use  are in Europe,  Brussels (Jonckheer et al VUB) ,  Paris (DiPaola et al Villejuif), and Wurtzberg, Germany (Reiners et al), where they continue to be used for clinical and research applications.

Improvements in ultrasound systems provide additional 3 D anatomic information that new make it possible to obtain more accurate system calibration data. This is needed due to decreasing XRF sensitivity with thyroid depth in the neck, due both to attenuation of incoming 60 keV photons, and outgoing absorption of emitted x-rays.  3D ultrasound provides good spatial data for compensation, as noted in work published by  Mardirossian, and  Reiners.  An improved direct coupling of XRF with ultrasound was developed in Reiners lab.  The development of high resolution 2-, and 3-D ultrasound probes, coupled with fine needle aspiration biopsy of nodules, reduce the need and interest in XRF for nodule characterization. An additional problem limiting its use is the difficulty dealing with radiation protection regulations due to the high activity transuranium source we used. Jim Patton’s thesis describes different systems we investigated for imaging stable and radioactive tracers, including novel applications of  X-ray fluorescence.

Patton, J.A., Hollifield, J.W., Brill, A.B., Lee, G.S., and Patton, D.D.: Differentiation Between Malignant and Benign Thyroid Modules by Fluorescent Scanning. J. Nucl. Med. 17: 17-21, 1976.

Patton, J.A., and Brill, A.B.:  Simultaneous Emission and Fluorescent Scanning of the Thyroid. Journal of Nuclear Medicine, Vol. 19, 464-469, 1978.

PATTON, J.A., SANDLER, M.P. and PARTAIN, C.L. (1985). “Prediction of benignancy of the solitary “cold” thyroid nodule by fluorescent scanning,” J Nucl Med. 26, 461-4.

LEE, G.S., SANDLER, M.P., PATTON, J.A. and BRILL, A.B. (1986). “Serial thyroid iodine content in hyperthyroid patients treated with radioiodine,” Clin Nucl Med. 11, 115-8.

Jonckheer M. and Deconinck F. X-ray Fluorescent Scanning of the Thyroid.  Martinos Nijhoff Publisher, 1983.

Mardirossian G, Matsushita T, Lei K, Clune T, Luo D, Karellas A, Botz E, and Brill AB, Calibration of X-ray Fluorescence Thyroid Imaging System. Physica Medica, 1996; 12: (2) 83-92

Reiners C, Sonnenschein W, Caspari G, Yavuz A, Ugur T, Lederbogen S, Olbricht T, Non-invasive measurement of thyroidal iodine content (TIC) by X-ray fluorescence analysis (XFA). Acta Med Austriaca. 1996;23(1-2):61-4.

Patton, James A., PhD  Physics 1972.  New Approaches to the Imaging of Distributions of Stable and Radioactive Tracers within the Body. Thesis.
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