Henrik Christian Bertelsen

Presurgical localization of abnormal parathyroid glands using a single injection of Tc-99m sestamibi: Comparison of high-resolution parallel-hole and pinhole collimators, and interobserver and intraobserver variation

Purpose Scintigraphy using Tc-99m sestamibi is sensitive in localizing abnormal parathyroid glands in patients with hyperparathyroid disease (HPT). Various methods have been described to increase the sensitivity of the single-tracer technique, such as SPECT, factor analysis of dynamic structures, and use of a pinhole collimator, but often the gain in sensitivity is accompanied by a loss of specificity. Purpose In this study, the authors compared the sensitivity and specificity of side localization of the diseased gland(s) using the double-phase single-tracer method performed with and without the addition of a pinhole collimator in the early and late phases of imaging. The combined high-resolution parallel-hole and pinhole collimator imaging protocol was further validated by investigation of interobserver and intraobserver variation. Materials and Methods Forty-seven patients with primary HPT and 16 patients with secondary HPT examined from 1996 to 1999 with the Tc-99m sestamibi double-phase technique and who had subsequent surgery formed the basis of the study. Their histologic and follow-up data were also factored into this analysis. Tc-99m sestamibi (750 to 900 MBq; 18.9 to 24.3 mCi) was injected. Ten-minute neck and mediastinum images acquiring 1,000 K counts were obtained with the high-resolution parallel-hole collimator, and a neck image containing 500 K counts was obtained with the pinhole collimator. Two to three hours later, the same parallel-hole and pinhole collimator images were obtained that had the same acquisition time as the early images. Two observers who were nuclear medicine specialists independently viewed all the parallel-hole scintigrams and afterward all parallel-hole and pinhole scintigrams two times. Results Thirty-eight (81%) of the patients with primary HPT had a single adenoma. The sensitivity and specificity for the correct side of localization were 54% and 89%, respectively, using the high-resolution parallel-hole collimator, and 88% and 77%, respectively, with the addition of the pinhole collimator in all patients with primary HPT. In patients with secondary HPT, the sensitivity and specificity for localization of the correct side were 58% and 100%, respectively, using the high-resolution parallel-hole collimator, and 85% and 100%, respectively, with the addition of the pinhole collimator. The interobserver agreement was acceptable, with an overall agreement of 84% and a &kgr; value of 0.67. The intraobserver agreement was even better, with an overall agreement of 88% and 90% and &kgr; values of 0.76 and 0.79 for the two observers. Conclusions Sensitivity is increased considerably when the pinhole collimator is added to the imaging protocol of parathyroid scintigraphy in patients with primary or secondary HPT. A loss of specificity occurred only in patients with primary HPT. The precision of the combined approach is very high.

Does radioiodine therapy have an equal effect on substernal and cervical goiter volumes? Evaluation by magnetic resonance imaging.

Most often thyroidectomy is recommended in patients with large goiters. However, high-dose (131)I therapy may be used in case of contraindications to surgery. Large goiters are often partially located in the mediastinum. The aim of this study was to evaluate the impact of (131)I therapy on the cervical and the substernal goiter volume, separately. Fourteen patients (median age, 69 years; range, 52-86 years) with a large multinodular goiter (three hyperthyroid) and with a substernal extension greater than 15 mL were included. T1-weighted magnetic resonance (MR) estimates of the thyroid volume in the cervical and substernal compartments were obtained before and 1 year after high-dose (131)I therapy. The total goiter volumes ranged from 182 to 685 mL. The median substernal volume was 66 mL (fraction of total volume, 17.6%; range, 8.0%-78.9%). One year after treatment, the median substernal goiter volume was reduced by 29.2% (range, -6.1%-59.4%, mean: 26.1% +/- 6.0%), and the cervical goiter volume by 30.3% (range, 6.0%-75.4%, mean, 35.6 +/- 5.6%) compared to baseline values; p = 0.25 for difference in a regional effect. The volume reduction was unrelated to initial substernal goiter size. Likewise, deterioration of the inspiratory capacity did not correlate with the magnitude of the substernal goiter extension. In conclusion, high-dose (131)I therapy seems as effective in reducing the substernal as the cervical goiter volume. However, because the overall effect is modest, this therapy should primarily be considered for the patient with a high surgical risk.

Prospective Multicenter Study of Bone Scintigraphy in Consecutive Patients With Newly Diagnosed Prostate Cancer

Background International guidelines uniformly suggest no routine staging of bone metastasis in patients with bone scintigraphy (BS) in low-risk prostate cancer (PCa). These recommendations are based on retrospective investigations only. In addition, BS has most often been reported as a definitive investigation with no room for equivocal cases. Objective The objective of this study was to determine the diagnostic value of BS in a large cohort of consecutive patients with newly diagnosed PCa. Design, Setting, and Participants Over a period of 1.5 years in 2008 to 2009, consecutive patients with newly diagnosed PCa were enrolled in a noninterventional, multicenter, observational study. All patients had a whole-body, planar BS. Clinical history and clinical, pathological, and biochemical data were obtained from electronic patient files and questionnaires. Outcome Measurements and Statistical Analysis Bone scintigraphy was classified into 4 categories as nonmalignant, equivocal, likely malignant, or multiple metastasis. The primary end point was final imaging, which was a composite end point of BS and additional CT and MRI investigations. Results and Limitations A total of 635 eligible patients were recruited. Their median prostate-specific antigen (PSA) was 15 ng/mL, median Gleason was 7, and 80% of patients had local disease (T1 or T2). The proportion of nonmalignant BS was 61%, equivocal scans 26%, and likely or definitive metastasis 13%. A total of 154 patients had additional CT or MRI investigations. The final imaging diagnosis showed a prevalence of bone metastases in 87 (13.7%) of 635 patients. No bone metastases were observed in (1) patients with PSA of less than 10 ng/mL, independently of the clinical Tstage and Gleason score (n = 212) and (2) PSA of less than 20 ng/mL if Tstage is less than T3 and Gleason score is less than 8 (n = 97). Approximately 50% of the patients enrolled in this study met these criteria. Conclusion This is the first prospective trial to demonstrate that BS can be avoided in patients with low-risk PCa.

Preoperative dual-phase parathyroid imaging with Tc-99m-sestamibi - Accuracy and reproducibility of the pinhole collimator with and without oblique images

Background: Previously, we have found that the additional use of a pinhole collimator in parathyroid scintigraphy resulted in a decrease in the number of incorrect side localizations and an increase in reproducibility compared with that of using a parallel-hole collimator alone. Purpose: The aim was to investigate whether the addition of anterior oblique views to parathyroid scintigraphy (PS) with a pinhole collimator could further enhance the diagnostic ability and reproducibility. The level of preoperative parathyroid hormone (PTH) as a potential predictor of the usefulness of the supplementary views was also studied. Method and Material: Forty-seven patients with primary hyperparathyroidism (HPT) underwent dual-phase PS using a combined protocol with parallel-hole and pinhole collimators. The pinhole collimator was used in the anterior as well as right and left anterior oblique positions. Thyroid pertechnetate scans were undertaken in the same positions. Two observers assessed the images independently. Results: By adding oblique views, the gain in correct side localization occurred in all cases but one was seen in patients with rapid washout. The level of PTH could not predict these patients. The observer agreement on correct side localizations rose significantly from 81% to 94%. Conclusion: The addition of oblique views to the imaging protocol using the pinhole collimator for parathyroid and thyroid scintigraphy in primary HPT results in an increase in observer agreement and the number of correct side localizations in patients with rapid washout of MIBI. The preoperative level of PTH cannot, however, predict these patients.

Observer agreement and accuracy in the evaluation of bone scans in newly diagnosed prostate cancer

ObjectiveThe aim of the study was to assess the agreement in the interpretation of bone scintigraphy (BS) in a newly diagnosed prostate cancer. Materials and methodsA total of 635 consecutive patients had their planar whole-body BS independently reviewed by three nuclear medicine physicians and classified by two grading systems: (a) a four-category scale (1: benign; 2: equivocal; 3: most likely malignant; and 4: multiple metastases) and (b) a dichotomous scale (bone metastasis present or absent). ResultsAgreement in the same category, or with one or two categories of differences, was found in 66, 34, and 1.3% of the readings, respectively. Average &kgr;-values were 0.59, 0.72, and 0.83 for unweighted, linear, and quadratic weighted variants, respectively. Very high agreement was observed (96% of the readings) with the dichotomous scale (average &kgr;=0.87); a comparison with a final imaging diagnosis with additional CT or MRI showed a sensitivity of 83% and a specificity of 98%. BS categories 1, 3, and 4 were consistent with the final imaging diagnosis in 96–99% of cases. The prevalence of metastasis was 10% in category 2. To optimize the diagnostic characteristics, category 2 should be regarded as a separate option. ConclusionClose agreement was found among trained observers for the evaluation of BS in prostate cancer. The high level of agreement with a dichotomous scale was hampered by diagnostic misclassification. A scale with equivocal findings on planar BS is considered important to allow for additional imaging and correct staging at the bone level of BS in a population with newly diagnosed prostate cancer.

Validation of contemporary guidelines for bone scintigraphy in prostate cancer staging: A prospective study in patients undergoing radical prostatectomy.

Abstract Objective: The aim of this study was to evaluate, using international urology and oncology guidelines, the criteria for performing bone scintigraphy (BS) in patients with newly diagnosed prostate cancer in a prospective setting with 2 years of follow-up after prostatectomy. Materials and methods: In a prospective setting, criteria from European and US urology and oncology guidelines were evaluated in 220 unselected patients with BS performed as a routine investigation before radical prostatectomy. A prostate-specific antigen level of 0.1 ng/ml or lower after surgery was considered successful and was used as a measure of true-negative BS. Results: Overall, 200 out of 220 patients (91%) experienced successful radical prostatectomy at 6 months, with a 2 year success rate of 83%. The proportion of redundant BS ranged from 56% to 89% among the guidelines, whereas the outcome after radical prostatectomy was 93% within 6 months after surgery and 86–89% after 2 years of follow-up, without significant differences among guideline recommendations. Conclusion: The guidelines from the American Urological Association and the criteria recently published by the present group proposed the largest proportion of redundant BS without compromising patient-related outcome.

Unexplained Bone Pain Is an Independent Risk Factor for Bone Metastases in Newly Diagnosed Prostate Cancer: A Prospective Study

OBJECTIVE To determine the relationship between bone pain and bone metastases in newly diagnosed prostate cancer. PATIENTS AND METHODS This prospective study of bone scintigraphy enrolled 567 consecutive patients with newly diagnosed prostate cancer. The presence of all-cause bone pain, known benign bone disease, and unexplained bone pain (ie, not related to known benign bone disease) was derived from a patient questionnaire. Univariate logistic regression models (LRMs) were used to assess the relationship between individual clinical variables (all-cause bone pain, unexplained bone pain, prostate-specific antigen, Gleason grade, T stage, and age) and bone metastases. A multivariate LRM was used to assess the relationship between bone metastases and all factors in combination. Agreement between the LRMs and bone metastases was estimated by accuracy and by Cohens κ. RESULTS All-cause bone pain predicted bone metastasis in univariate but not multivariate analysis. Unexplained bone pain remained an independent predictor of bone metastases in multivariate analysis (odds ratio: 4.5; P < .001). Prostate-specific antigen was the single most important predictor of bone metastases (P < .001). CONCLUSION Unexplained bone pain was a strong independent risk factor for bone metastasis. Guidelines should recommend staging bone scintigraphy in patients with unexplained bone pain, regardless of other risk factors.

Computer-assisted interpretation of planar whole-body bone scintigraphy in patients with newly diagnosed prostate cancer

PurposeThe aim of this study was to compare the diagnostic properties of EXINI BoneBSI in newly diagnosed prostate cancer in comparison with expert reading. Materials and methodsBone scintigraphy was performed in consecutive patients referred for staging at three clinics (342 patients with DICOM file format, 272 with Interfile format). Images were reported by three independent readers on a four-point scale (class 1–4) and by using a dichotomous outcome (M1 or M0). The software analyzed data in balanced mode, as well as using ‘patient-specific’ settings (based on tumor characteristics), and classified outcome as normal (N), probably normal (pN), probably abnormal (pA), and abnormal (A). ResultsClassification of bone metastasis using the software (pA+A) versus experts (class 3+4) showed a sensitivity of 93.3%, specificity of 89.3%, positive predictive value of 57.5%, and negative predictive value of 98.9% with DICOM files. The diagnostic properties of the software were notably different with Interfile format. For example, expert M1 versus software A showed a sensitivity of 90.0%, specificity of 98.9%, positive predictive value of 88.2%, and negative predictive value of 98.3% with DICOM files, versus 69.2, 88.2, 38.3, and 96.4% with Interfile format, respectively. Generally, patient-specific settings did not influence the diagnostic characteristics of the software versus balanced setting with expert reading as reference. ConclusionEXINI BoneBSI showed high sensitivity and specificity for bone metastasis in patients with newly diagnosed prostate cancer. The software ruled out metastasis with confidence, whereas the positive predictive value was modest. The diagnostic properties were different for DICOM and Interfile file formats.

Prospective evaluation of computer-assisted analysis of skeletal lesions for the staging of prostate cancer

BackgroundThe purpose of this study was to compare the agreement of the bone scan index (BSI) using EXINI BoneBSI versus experts’ readings in the initial staging for bone metastasis in prostate cancer. In addition, the diagnostic outcome was assessed in a large subset of patients where a true reference for metastases could be determined based on clinical and biochemical follow-up and/or supplementary imaging.MethodsA total of 342 patients had a bone scintigraphy as part of routine staging for prostate cancer. Supplementary imaging was obtained at the discretion of the referring urologist. After full recruitment, the BSI and the number of malignant lesions were calculated using EXINI BoneBSI, and three imaging experts independently classified bone status by a dichotomous outcome (M1 for bone metastasis, M0 for no bone metastasis). A true reference was available in a subset of the patients based on post-operative prostate-specific antigen responses after radical prostatectomy and/or supplementary imaging.ResultsSoftware analysis with a BSI > 0 as the cut-off for metastasis showed excellent agreement with expert classification for M1 disease (96% of the patients) but modest agreement for M0 disease (38%). With a BSI > 1, the agreement was 58% for M1 and 98% for M0. Software analyses based on individual European Association of Urology risk classification did not improve the diagnostic performance. Among patients with a true reference, the software showed metastasis in 64% of the M0 patients but correctly classified metastases in all M1 patients. The sensitivity was 100%, the specificity was 36%, the positive predictive value was 12.6% and the negative predictive value was 100% with a BSI >0 compared with 66.7%, 97.8%, 72.7%, and 97.0% with a BSI > 1.ConclusionThe diagnostic value of using EXINI Bone for the BSI in the staging of newly diagnosed prostate cancer is limited.

Supernumerary parathyroid glands in recurrent secondary hyperparathyroidism.

Disease recurrence, after initially successful parathyroid surgery, is very common in patients undergoing periodic hemodialysis. The expected diagnosis is hypertrophy of the parathyroid transplant or of the partially resected gland. In addition, repeated operation may be necessary if the surgeon fails to locate multiple ectopic or supernumerary abnormal glands on initial surgery. Parathyroid scintigraphy does not always show the true number of abnormal glands on the first scan, but after removal of the visualized abnormal glands, the remaining parathyroid tissue will presumably become more prominent on sestamibi imaging. Sestamibi parathyroid imaging is recommended as the first-line imaging procedure in patients with recurrent secondary hyperparathyroidism.