Parathyroid Imaging: The Importance of Pinhole Collimation with Both Single- and Dual-Tracer Acquisition

Patient Database

The parathyroid imaging studies were derived from a previously published series of 37 consecutive patients with surgically proven parathyroid adenomas (18). Four of the patients in the previous series had ectopic adenomas and were excluded because the adenomas were outside the field of view of the pinhole image. No patients were eliminated because they had had previous parathyroid or thyroid surgery or were taking thyroid replacement hormone. The study was approved by the Colorado Multiple Institutional Review Board.

Imaging Protocol

Patients were initially given 22.2 MBq (600 μCi) of ¹²³I orally. Two hours later, the patients were given 925 MBq (25 mCi) of ^99mTc-sestamibi intravenously. Dual-phase imaging was performed at 15 min and at 3 h after administration of the ^99mTc-sestamibi. The images were acquired with a dual-head e.cam γ-camera with an energy resolution of 9% (Siemens Medical Solutions). The camera was configured with a pinhole collimator on one head and a low-energy high-resolution collimator on the other head. At each time, 5-min pinhole images of the neck in the anterior and both anterior oblique projections (45°) were obtained with a 4-mm pinhole insert. In addition, at both times a 5-min low-energy high-resolution parallel-hole collimator image with a field of view extending from the submandibular glands to the left ventricle was obtained in the anterior projection.

The ^99mTc-sestamibi and ¹²³I images were acquired simultaneously with a 12% energy window centered at 140 keV for ^99mTc-sestamibi and an 8% energy window centered at 159 keV for ¹²³I (3). There was no correction for cross talk (1,16). Subtraction images were constructed for all pairs of ^99mTc-sestamibi and ¹²³I pinhole images. The subtractions were done manually by increasing the amount of subtraction of the ¹²³I thyroid image from the ^99mTc-sestamibi image until the thyroid was essentially no longer visible.

Image Processing

Because, in our routine protocol, the parallel-hole collimator image is obtained in only the anterior projection, only the anterior pinhole image was used in all comparisons. Also, in our routine protocol anterior parallel-hole images are obtained for both ^99mTc-sestamibi and ¹²³I but no subtraction image is generated. For the purposes of this study, an anterior parallel-hole subtraction image, ^99mTc-sestamibi minus ¹²³I, was generated at 15 min only for each patient study. All subtractions were done manually. The algorithm was to subtract the ¹²³I image from the ^99mTc-sestamibi image until the thyroid was just removed, leaving a salt-and-pepper appearance to the thyroid bed. Each of the pinhole and parallel-hole collimator images was processed so that the field of view was square and so that the thyroid filled approximately three quarters of the field of view.

Image Sets

The images from each patient study were used to create 4 image sets. The first image set consisted of anterior images of ^99mTc-sestamibi at 15 min and at 3 h acquired with a pinhole collimator (Figs. 1 and 2). The second image set was the same as the first except that the images were acquired with a parallel-hole collimator. The third and fourth image sets consisted of the first 2 image sets plus the corresponding pinhole or parallel-hole collimator anterior subtraction image (Figs. 1 and 2).

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FIGURE 1.

Pinhole collimator (A) and parallel-hole collimator (B) images of ^99mTc-sestamibi at 15 min and 3 h, and image of ^99mTc-sestamibi minus ¹²³I at 15 min, in patient with hyperparathyroidism and 380-mg parathyroid adenoma located inferiorly on right. With pinhole collimation, 2 observers correctly localized adenoma without and with subtraction image with degree-of-certainty grades of 2 and 3 for one observer and 3 and 3 for the other. With parallel-hole collimation, observers did not identify adenoma without subtraction image and did localize adenoma with subtraction image with grades of 1 and 1.

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FIGURE 2.

Pinhole collimator (A) and parallel-hole collimator (B) images of ^99mTc-sestamibi at 15 min and 3 h, and image of ^99mTc-sestamibi minus ¹²³I at 15 min, in patient with hyperparathyroidism and 1,010-mg parathyroid adenoma located inferiorly on right. With pinhole collimation, 2 observers correctly localized adenoma without and with subtraction image with degree-of-certainty grades of 3 and 2 for one observer and 3 and 3 for the other. With subtraction image, one observer located adenoma at middle level whereas other localizations were all inferior. With parallel-hole collimation, only one observer identified adenoma without subtraction image, grades of 0 and 1, and both observers localized adenoma with subtraction image with grades of 1 and 1.

Two groups of images were created for interpretation. The first group was created by combining the first and second image sets, single-tracer dual-phase (ST-DP), with either pinhole or parallel-hole collimation in random order. The second group was created by combining the third and fourth image sets, single-tracer dual-phase plus subtraction (ST-DP + S), with either pinhole or parallel-hole collimation in random order. Thus, each patient was present twice in each of the 2 image interpretation groups, once with pinhole images and once with parallel-hole images (Figs. 1 and 2).

Image Interpretation

Two experienced nuclear medicine physicians independently interpreted the 2 groups, first the ST-DP image set and then the ST-DP + S image set. The observers were masked to all patient identification and to the type of collimation used for image acquisition. There was at least 1 mo between interpretations of the 2 groups for both physicians.

The images were interpreted on a 4-point scale, with zero indicating no evidence of a parathyroid adenoma and 1 through 3 indicating a focus of activity consistent with a parathyroid adenoma. A grade of 1 indicated a possible parathyroid adenoma, 2 a probable parathyroid adenoma, and 3 a definite parathyroid adenoma. In addition to the certainty of a parathyroid adenoma, the interpreting physician indicated the location of the abnormality with respect to side (right or left) and location with respect to the thyroid lobes (superior, middle, or inferior to the thyroid). If a patient’s images showed more than one parathyroid abnormality, the interpretation process was repeated for each abnormality beginning with the most obvious abnormality. If an observer identified an incorrect location (false-positive) and did not grade the correct location, the correct location was assigned a 0.

Surgery

All operations were performed by 1 of 2 endocrine surgeons and 2 otolaryngologic surgeons. Intraoperative assays of serum parathormone were done at the beginning of surgery and after the removal of each parathyroid gland. An intraoperative decrease in blood parathormone level of at least 50% was considered evidence of curative surgery. The surgical finding, including intraoperative parathormone values, and the histopathologic findings were used as diagnostic proof.

Pathologic Diagnosis

The diagnosis was based primarily on the presence of hypercellularity.

Statistical Analysis

Sensitivity, the primary outcome, was defined as the proportion of locations of parathyroid adenomas that were correctly identified. The site location was coded as correct if the observer’s response matched the surgical result exactly or within half the distance between the inferior and superior pole to allow for variation in the accuracy of the surgical description. Thus, an imaging location of middle thyroid was considered to match a surgical location of superior or inferior and vice versa. The number of times a middle location by imaging was counted as correct in comparison to a superior or inferior location by surgery and vice versa was quantified for each observer.

Specificity is difficult to calculate because the observers knew that each patient had at least one adenoma. In addition, it is considered good practice in the interpretation of parathyroid imaging studies to mention possible secondary adenomas in case there are multiple adenomas (1). At the time of surgery, if the serum parathormone level does not decrease by 50% after removal of the first adenoma, the surgeon then has a guide to the location of a likely second adenoma. However, the number of false-positive localizations was determined for each observer for pinhole and parallel collimation with and without subtraction images and served as an indicator of specificity.

The sensitivity of the 4 protocols was compared statistically using a pseudo-likelihood estimate for the 6 pairwise differences between the 4 protocols (parallel and pinhole methods, each with and without subtraction) in a repeated-measures model for the binary outcome (19). Observer and protocol were entered as main effects; patient was designated as a repeated effect. Descriptive statistics for the number of lesions located, the sensitivity rate, and its 95% exact binomial confidence interval were also computed. A similar model was used to evaluate the certainty score (0, 1, 2, or 3) in a multinomial model for the ordered responses (19). Again, observer and protocol were entered as main effects; patient was designated as a repeated effect.