Image normalization and background subtraction in T1-201/Tc-99m parathyroid subtraction scintigraphy. Effect on lesion detection.

The authors have developed two computer algorithms for T1-201/Tc-99m parathyroid subtraction scintigraphy that was performed on patients who subsequently underwent surgical exploration of the neck. Both methods employed a region-of-interest drawn around the thyroid/parathyroid glands for image realignment. The first algorithm normalized the Tl-201 and Tc-99m images using the ratio of maximum counts over the thyroid in each image. The second computer algorithm incorporated Tl-201 image background correction and normalization by the average of the ratios of maximum counts computed over each quadrant in both images. In 10 patients with confirmed parathyroid adenomas or hyperplasia, the first method yielded a 44% sensitivity. Upon reanalysis with the second algorithm, the sensitivity improved to 100%. Subsequently, in a total of 22 patients with 30 abnormal glands analyzed with the second algorithm, a sensitivity of 80% (94% for adenoma and 62% for hyperplasia) was achieved, with a specificity of 91%, as confirmed by surgery.     

Localization of abnormal parathyroid gland(s) using thallium-201/iodine-123 subtraction scintigraphy in patients with primary hyperparathyroidism

Tl-201/I-123 subtraction scintigraphy was performed in 17 patients with clinical symptoms and biochemical measurements suggestive of primary hyperparathyroidism. Nineteen abnormal sites were identified. These results were correlated with PTH measurements and surgical findings. Three sites were considered unrelated to the parathyroid glands, two corresponding to palpable thyroid nodules and one to muscle uptake of unknown origin. One scintigram did not reveal either of two abnormal glands while two others were considered falsely positive in view of surgical failure. Fourteen sites corresponded to abnormal parathyroid gland at surgery; five glands, weighing more than 2000 mg, could be correctly located on the Tl-201 scintigraphy prior to the subtraction procedure; six glands, weighing between 500 and 2000 mg, were easily localized after the subtraction procedure; three glands, weighing between 180 and 200 mg, were correctly localized after further manipulation of the subtraction procedure. In a patient with parathyroid hyperplasia, one gland, weighing 150 mg, was not located and another was not found upon surgery. Overall sensitivity was 87.5%. A positive correlation between PTH levels, tumor weight, and ease of detection on scintigraphy was found. This correlation was particularly useful in excluding large abnormal uptake related to thyroid disorder or artifact. The results suggest that Tl-201/I-123 parathyroid scintigraphy could become an alternative to Tl-201/Tc-99m parathyroid scintigraphy, with possibly improved detection of low weight abnormal parathyroid glands.     

Tl-201 uptake in brown tumors of hyperparathyroidism.

Tl-201 chloride bone scans were performed on nine patients with primary hyperparathyroidism just after Tl-201 and Tc-99m parathyroid subtraction scintigraphy. Bone lesions accumulate Tl-201, especially in sites of brown tumor formation. This was proven by the histopathologic examination of two patients. Eight patients had bone scans with Tc-99m MDP. The lesion-to-background ratio was quantified in seven patients for Tl-201 and in four patients for Tc-99m MDP. Tl-201 uptake of the lesions were quantified in two patients. The lesion-to-background ratio was 1.63 +/- 0.21 and 2.51 +/- 0.88 for Tl-201 and Tc-99m MDP, respectively. A Ga-67 citrate scan was performed on one patient, and the lesion-to-background ratio was 1.49 +/- 0.06. The accumulation of Tl-201 in brown tumors of bone might be due to increased blood flow and local metabolic activity. Tl-201 chloride was inferior to Tc-99m MDP in lesion detection. It is concluded that bone imaging with Tl-201 can easily be performed following parathyroid subtraction scintigraphy to delineate the sites of brown tumor formation.     

Brown tumor of the sternum: a potential source of false-positive Tl-201 and Tc-99m subtraction imaging in the mediastinum

Tl-201 and Tc-99m subtraction imaging is a well-established technique for detecting parathyroid adenomas. We report a case of a brown tumor of the upper sternum mimicking an ectopic mediastinal parathyroid adenoma on Tl-201 and Tc-99m subtraction imaging in a patient with hyperparathyroidism. This brown tumor showed Tl-201 uptake but not Tc-99m uptake and thus did not subtract out in this scan.     

Radionuclide imaging of parathyroid tumors: historical perspectives and newer techniques

The increasing use of automated blood chemistry screens for serum calcium levels along with improved methods in measuring parathyroid hormone (PTH) levels have made the diagnosis of parathyroid disease a common clinical problem. Parathyroid adenomas account for the majority of primary hyperparathyroidism with diffuse hyperplasia and parathyroid carcinoma occurring less frequently. Early scintigraphic techniques to identify enlarged parathyroids used selenomethionine-75 which was considered to be incorporated into PTH. In general, the sensitivity of scanning the neck using this tracer was related to the size of the enlarged parathyroid, but in large series, the overall sensitivity was less than 50%. Recent work by Ferlin et al, using a Technetium-99m/Thallium-201 subtraction scintigraphic technique has yielded a sensitivity of 92% in identifying pathologically enlarged parathyroid glands. Winzelberg et al modified this technique to allow imaging the mediastinum plus simplifying the subtraction method. In a prospective study with high-resolution sonography, similar sensitivities and specificities were found with sonography and scintigraphy. Tl-201/Tc-99m pertechnetate subtraction scintigraphy appears to be an accurate technique in identifying pathologic parathyroid enlargement. Its ultimate role in the evaluation of patients with suspected hyperparathyroidism still needs to be determined.     

New perspectives for diagnosis of nodular goiter by technetium-thallium subtraction scanning

To improve the scintigraphic differential diagnosis of thyroid nodules, Tc-99m pertechnetate-Tl-201 Cl subtraction scintigraphy (Tc-Tl subtraction scanning) was performed in 106 patients with various histologically proven thyroid nodules. Results were evaluated by comparison with surgical findings and preoperative ultrasonographic results. Thyroid nodules were more successfully detected by Tc-Tl subtraction scanning than by either Tc-99m pertechnetate or Tl-201 Cl scintigraphy alone. Detection of nodules was further improved when images recorded by the three methods were integrally observed (sensitivity 83%, accuracy 89%), with detectability approaching that of ultrasonography. False-positive or -negative Tc-Tl subtraction scans were obtained principally when multiple nodules were present (7 cases) or when no discrepancy existed between the accumulations of Tc-99m pertechnetate and Tl-201 Cl (18 cases). Most colloid nodules exhibited irregular margins, heterogeneous internal accumulations of Tl-201 Cl, and distorted shapes on Tc-Tl subtraction scans, while the majority of adenoma were oval-shaped with smooth margins. Carcinoma were characterized by homogeneous internal accumulation of Tl-201 Cl and distorted shapes.     

Comparison of Tl-201 renal uptake with Tc-99m DTPA angiorenography in patients with hypertension. Measures of renal asymmetry.

Renal uptake of Tl-201 reflects renal perfusion and may have a role in defining renal asymmetry in patients with hypertension who are referred for myocardial scintigraphy. The authors compared two methods of quantitating differential renal uptake of Tl-201, with similar data obtained from the angiographic and renal uptake (RU) phases of Tc-99m DTPA scintigraphy in 35 patients with hypertension. For Tl-201, asymmetry in renal counts was quantitated based on a simple outline technique or on interpolative background subtraction of 5-minute posterior images. Inter-observer and intra-observer variability among duplicate measurements were lower for Tl-201, particularly with interpolative background subtraction, than for Tc-99m DTPA. Renal/background ratios were similar for Tl-201 and RU-phase Tc-99m DTPA images when considering liver, spleen, or inter-renal regions as background; however, paraspinal uptake was relatively higher with Tl-201 (P less than 0.01). Qualitatively, renal asymmetry scores with the two radiotracers agreed (r = 0.89, blinded readings by four observers), although asymmetry was more marked with Tl-201 (P = 0.06). Measurements with Tl-201 agreed with both phases of Tc-99m DTPA (r = 0.96 to 0.98), but interpolative background subtraction systematically yielded greater inter-renal asymmetry than RU (P less than 0.01), reflecting the qualitative impression. Thus, ancillary Tl-201 imaging reflects differences between the kidneys in a fashion similar but not identical to Tc-99m DTPA scintigraphy.     

Dynamic or early imaging in dual-tracer parathyroid scintigraphy

The dual tracer radionuclide method using Tl-201 and Tc-99m subtraction imaging has proven to be effective for evaluation of parathyroid lesions. Ninety-two percent sensitivity for detection of parathyroid adenomas has been reported. The importance of dynamic or early imaging, however, has not been emphasized. A case of surgically proven parathyroid adenoma was detected using dynamic scanning after Tl-201 injection and was less apparent on delayed image due to rapid washout.     

Localization of hyperfunctioning parathyroid glands by means of thallium-201 and iodine-131 subtraction scintigraphy in patients with primary and secondary hyperparathyroidism

The accuracy of the preoperative localization of hyperfunctioning parathyroid glands by subtraction scintigraphy with 201Tl and 131I was evaluated by comparison with the operative findings. The subjects were 67 consecutive patients with hyperparathyroidism (HPT), including 24 with primary and 43 with secondary HPT. In primary HPT, surgery revealed 26 adenomas weighing 0.26-15.80 g (mean +/- SD; 3.01 +/- 3.04 g). Two patients had double adenomas. Scintigraphy correctly localized 25/26 adenomas (96.2%) in primary HPT for a sensitivity, specificity, and accuracy of 96.2%, 98.5%, and 97.9%, respectively. In secondary HPT, 163 hyperplastic glands weighing 0.03-5.08 g (0.85 +/- 0.93 g) were found. Scintigraphy correctly localized 79 glands (48.5%) weighing 0.03-5.08 g (1.19 +/- 1.10 g), but 84 glands (51.5%) weighing 0.04-2.70 g (0.51 +/- 0.50 g) were not detected. Thus, the sensitivity, specificity, and accuracy of scintigraphy were respectively 48.5%, 100%, and 51.2%, in secondary HPT. These results show that scintigraphy with 201Tl and 131I can be used to locate abnormal parathyroid glands with an efficacy equal to or better than that of the conventional methods with 201Tl and 99mTc or 201Tl and 123I.     

Comparison between 99mTc-tetrofosmin/pertechnetate subtraction scintigraphy and 99mTc-tetrofosmin SPECT for preoperative localization of parathyroid adenoma in an endemic goiter area

RATIONALE AND OBJECTIVES: Technetium-99m-((99m)Tc-) tetrofosmin, a cationic, lipophilic complex like (99m)Tc-sestamibi, has proved to be a potential tracer for parathyroid scintigraphy despite some differences in washout behavior from the thyroid gland. Previous results comparing a double-phase technique with single-proton emission computed tomography (SPECT) or with subtraction techniques demonstrated a high detection rate, especially when SPECT and subtraction techniques were used, whereas the double-phase protocol revealed only moderate results. In this study, a direct comparison was made between (99m)Tc-tetrofosmin/pertechnetate subtraction and SPECT to elucidate the optimal protocol for tetrofosmin parathyroid imaging. METHODS: Twenty-three patients who were biochemically suspected of parathyroid adenoma or hyperplasia due to primary or tertiary hyperparathyroidism were included in our study. In all patients, serum calcium, phosphate, and intact parathormone levels were analyzed in a single blood sample before (99m)Tc-tetrofosmin/pertechnetate subtraction scintigraphy and SPECT. Ultrasound of the neck was performed in all patients to exclude false-positive results due to thyroid adenomas. All patients underwent parathyroidectomy with intraoperative revision of all parathyroid glands, and the histological results were compared with preoperative findings. RESULTS: Both imaging modalities, ie, subtraction scintigraphy and SPECT, correctly identified 20 of 23 (87%) histologically confirmed adenomas preoperatively. The positive predictive value was calculated to be 95% and 100%, respectively, for these two methods. Subtraction scintigraphy and SPECT showed concordant results in 19 patients (18 positive, 1 false-negative) and discordant results in 4 patients (2 positive with subtraction, 2 with SPECT). The combined use of subtraction scintigraphy and SPECT techniques revealed a sensitivity of 95.7% (22/23) and a positive predictive value of 95%. The whole procedure can be performed in less than 90 minutes per patient. Whereas subtraction scintigraphy tended to show more false-positive retentions due to thyroid adenomas, the interpretation of SPECT may be difficult in small adenomas with missing thyroid/parathyroid differential washout. CONCLUSIONS: Both imaging modalities, subtraction scintigraphy with pertechnetate and SPECT, are highly sensitive methods for parathyroid adenoma localization with (99m)Tc-tetrofosmin. However, our study did demonstrate that a combination of both modalities can further improve the diagnostic accuracy. Especially in an endemic goiter area, additional ultrasound may be required to avoid false-positive results due to thyroid adenomas.     

New perspectives in localizing enlarged parathyroids by technetium-thallium subtraction scan

Double-tracer scanning (Tc-99m as pertechnetate and Tl-201 as chloride) with an Anger camera and computerized image subtraction was performed in 61 patients whose clinical and biochemical findings had suggested primary hyperparathyroidism. This study showed intra- or extrathyroidal focal uptake of thallium in 37 cases. Among these, 24 patients underwent surgery, and 18 parathyroid adenomas, five carcinomas, and one hyperplastic gland were found exactly in the sites predicted by scintigraphy. Among 24 patients with negative scans, only two underwent surgery; a hyperplastic parathyroid gland (diam less than 0.5 cm) was found in both. The success rate was 92% in the cases in which operation was performed. We believe that the new method may be useful in the preoperative detection of parathyroid enlargements.     

Parathyroid imaging: comparison of double-tracer (T1-201, Tc-99m) scintigraphy and high-resolution US

Parathyroid scintigraphy using a double-tracer (T1-201, Tc-99m) subtraction technique depicted 17 of 23 (74%) parathyroid adenomas in patients with and without previous neck operations. High-resolution (10-MHz) ultrasound (US) depicted 18 (78%) of these adenomas. Average tumor size depicted by US was 17 X 10 X 8 mm (excluding a giant adenoma) and 19 X 10 X 9 mm by scintigraphy. Alone, neither modality was particularly sensitive in the depiction of primary hyperplasia of the parathyroid glands, but combined techniques were more effective than the use of a single modality. With both US and T1-201 scintigraphy, only two of 23 cases of parathyroid adenoma in the neck were missed, and none of the eight cases of secondary hyperplasia were missed. In 11 patients who had previously undergone neck surgery, parathyroid tumors were identified in eight by either US or double-tracer scintigraphy. Preoperative parathyroid imaging with double-tracer scintigraphy and high-resolution US is suggested for patients with hyperparathyroidism, particularly in those patients who have had previous parathyroid surgery.     

Ectopic parathyroid gland. Localization with thallium-201 SPECT

Dual isotope Tl-201/Tc-99m subtraction is a useful technique for localization of abnormal parathyroid glands. A case of tomographic localization of nonsubtracted Tl-201 to a mediastinal parathyroid is reported and the possible benefit of this method discussed.     

A parathyroid cyst with adenoma on thallium-201/technetium-99m subtraction imaging

A case of a parathyroid cyst with adenoma was seen on Tl-201/Tc-99m subtraction imaging. The literature regarding parathyroid cysts and the subtraction technique for parathyroid adenoma imaging was reviewed.     

Pre-operative sestamibi-technetium subtraction scintigraphy in primary hyperparathyroidism: experience with 156 consecutive patients.

AIM: The aim of this study was to assess the usefulness of pre-operative sestamibi-technetium subtraction scintigraphy in a large cohort of patients with primary hyperparathyroidism (HPT). MATERIALS AND METHODS: A group of 156 consecutive patients with biochemically proven HPT underwent sestamibi-technetium subtraction scintigraphy before cervical exploration. Images were interpreted and reported prospectively and influenced the extent of surgical exploration. The intraoperative findings were compared retrospectively with the pre-operative scintigram reports in 154 individuals with technically satisfactory scintigrams. RESULTS: Of the 154 patients with satisfactory scintigrams, 122 (78.2%) demonstrated a single focus of activity following subtraction, 31 (19.9%) had negative findings and the remaining scintigram showed four foci of activity. At operation 138 (89.6%) solitary adenomas were removed, 13 patients (8.4%) had multi-gland disease and in three individuals (2.0%) no abnormal parathyroid tissue was found. The pre-operative scintigram accurately localized 91 of 98 (92.9%) solitary tumours weighing > 500 mg but only 18 of 35 (51.4%) adenomas weighing < 500 mg, (P < 0.0001). Overall sensitivity of sestamibi-technetium scintigraphy for localizing single parathyroid adenomas was 83.7%. CONCLUSION: Sestamibi-technetium subtraction scintigraphy will accurately localize a high proportion of solitary parathyroid adenomas but its usefulness is diminished by its inability to consistently identify smaller tumours.     

The usefulness of radio-guided surgery in secondary hyperparathyroidism

Recent reports have shown that radio-guided surgery with an intraoperative gamma probe (IGP) is useful for identifying parathyroid adenomas. The aim of this study was to evaluate the usefulness of IGP mapping in patients with secondary hyperparathyroidism. Seven patients with secondary hyperparathyroidism underwent technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) scintigraphy immediately before undergoing surgical resection of all parathyroid tissues. We compared the sensitivity of Tc-99m MIBI scintigraphy alone with that of the combination of Tc-99m MIBI scintigraphy and IGP mapping. The sensitivity of the combination of Tc-99m MIBI scintigraphy and IGP mapping was 100% (28 of 28 lesions) and was significantly higher than that of Tc-99m MIBI scintigraphy alone (71.4%, 20 of 28 lesions). The combination of the Tc-99m MIBI scintigraphy and IGP mapping has increased sensitivity for identifying parathyroid lesions during parathyroidectomy in patients with secondary hyperparathyroidism.     

Comparative evaluation of Tc-99m MIBI and Tl-201 chloride SPECT in non-small-cell lung cancer mediastinal lymph node metastases

PURPOSE: To compare the utility of Tc-99m MIBI SPECT and Tl-201 chloride SPECT for presurgical assessment of lung cancer mediastinal lymph node metastases. METHODS: Forty-one patients with non-small-cell lung cancer underwent dual-isotope imaging with Tl-201 chloride and Tc-99m MIBI and were evaluated for mediastinal lymph node involvement. RESULTS: The sensitivity rates of early and delayed Tc-99m MIBI SPECT and of early and delayed Tl-201 chloride SPECT for detecting mediastinal nodal metastases were 69%, 69%, 92%, and 92%, respectively. The corresponding specificity rates were 96%, 96%, 93%, and 96%. CONCLUSION: Tl-201 chloride SPECT is superior to Tc-99m MIBI SPECT when used to detect mediastinal lymph node metastases in patients with non-small-cell lung cancer.     

Diagnostic dilemmas in parathyroid scintigraphy.

PURPOSE: Tc-99m MIBI scintigraphy can be useful for preoperative localization of parathyroid adenomas, despite its limited sensitivity. To refine interpretation, the authors conducted prospective reviews of the scintigraphic studies of patients with concomitant thyroid nodular disease and revised the false-negative and false-positive results. MATERIALS AND METHODS: Seventy-seven patients with primary hyperparathyroidism, associated with a solitary parathyroid adenoma, underwent dual-phase MIBI scintigraphy with subsequent injection of Tc-99m pertechnetate before surgery. The false-negative and false-positive scintigraphic findings were identified and revised. RESULTS: After surgery, revision of 19 false-negative scans of the total 77 studies led to the demonstration of an adenoma in seven patients. In five of the seven studies, the adenoma had been overlooked as a result of rapid tracer washout. Two additional small focal lesions would have also been identified if subtraction had been used for differences in contour of the MIBI and pertechnetate images. Four studies were interpreted falsely as abnormal, leading to a positive predictive value of 91%; three were associated with thyroid nodular disease. CONCLUSIONS: Differential washout of MIBI from thyroid and parathyroid tissue is not universal. When MIBI is washed out rapidly from parathyroid adenomas, subtraction of a thyroid image should be performed and differences in contour delineated to localize the adenoma accurately. Some, but not all, thyroid lesions account for the false-positive findings.     

Early and delayed imaging of Tc-99m HMPAO versus Tl-201 in benign and malignant thyroid tumors. Similar uptake but different retention.

The authors performed both Tc-99m HMPAO and Tl-201 scintigraphy in 30 patients with thyroid tumors (21 papillary adenocarcinoma, three solid follicular adenoma, six adenomatous goiter with cystic degeneration). Increased accumulation of both Tc-99m HMPAO and Tl-201 was seen in 14 patients with papillary adenocarcinoma and three with solid follicular adenoma, whereas two patients with papillar adenocarcinoma had low accumulation of both tracers. Of the six patients with adenomatous goiter with cystic degeneration, four had low accumulation of both Tc-99m HMPAO and Tl-201, and one patient had low accumulation of Tc-99m HMPAO only. Iso accumulation (same accumulation as the normal thyroid) of Tc-99m HMPAO was seen in five patients with papillary adenocarcinoma and one with adenomatous goiter. The distribution of Tc-99m HMPAO in the thyroid tumors and normal thyroid tissue was independent of time from 2 to 120 minutes after injection. The results of dynamic studies using Tc-99m HMPAO suggested that the accumulation of Tc-99m HMPAO in thyroid tumors reflected mainly tumor blood flow. The resultant Tc-99m HMPAO images were essentially similar to the Tl-201 images obtained 10 minutes after injection. Tc-99m HMPAO imaging can be a suitable substitute for Tl-201 imaging, and it may possibly be used to estimate tumor blood flow in patients with thyroid tumors.     

Tc-99m sestamibi scanning in the preoperative localization of mediastinal parathyroid adenomas

We report on two patients with mediastinal parathyroid adenomas who underwent preoperative Tc-99m sestamibi scintigraphy. Excellent physical characteristics of technetium and slow washout of Tc-99m sestamibi made possible clear delineation of mediastinal parathyroid adenomas by Tc-99m sestamibi imaging.