False-negative Scans Research Articles

Low-grade chondrosarcomas: a difficult target for radionuclide imaging. Case report and review of the literature

Bone scan with Tc-99m (technetium) diphosphonate is sensitive, but non-specific for musculoskeletal tumors. Tl-201 (thallium), Tc-99m-sestamibi, Tc-99m-tetrofosmin, and F-18-fluorodeoxyglucose (F-18-FDG) can visualize tumors more specifically and are therefore useful in orthopedic oncology. However, cartilaginous tumors are characterized by histological and biological features, which potentially impair specific radionuclide imaging. A case of a patient with a low-grade primary chondrosarcoma of the femur and a false negative Tl-201 scan is presented. Tc-99m-based tumor-localizing compounds (sestamibi, tetrofosmin), as well as metabolic and receptor-imaging radiopharmaceuticals have also been reported to fail in low-grade chondrosarcomas imaging. Low cellularity, mitochondrial specialization and the presence of an efflux membrane pump may contribute to poor imaging. A negative Tl-201 or Tc-99m-sestamibi scan should be interpreted with caution, when the possibility of a chondrosarcoma is not negligible.

Reduction of Myocardial 2-Deoxy-2-[ 18F]Fluoro- D-Glucose Uptake Artifacts in Positron Emission Tomography Using Dietary Carbohydrate Restriction

Purpose: The use of carbohydrate restriction prior to 2-deoxy-2-[ 18F] positron emission tomography (FDG-PET) to reduce image artifacts caused by myocardial FDG uptake was investigated. Procedures: Ninety-six whole-body FDG-PET scans were studied. Dietary intake of the meal prior to scanning was recorded. Coronal and transverse images were assessed visually and scored based on myocardial FDG uptake and the presence of associated image artifacts. Results: Of 49 patients who consumed carbohydrates prior to PET, 14 (28.6%) had a clinically significant image artifact versus only five (10.6%) of 47 patients who did not consume carbohydrates ( P = 0.0275). A 3.36 times increased risk (confidence interval 1.00–12.97) for clinically significant image artifacts was calculated for patients who consume carbohydrates in their last meal prior to scanning. Conclusions: With the rising use of FDG-PET in the evaluation of intra-thoracic malignancies, dietary carbohydrate restriction prior to scanning may play a role in increasing lesion detectability and reducing false negative scans. (Mol Imag Biol 2002;4:232–237)

Diagnostic dilemmas in parathyroid scintigraphy.

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. 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. 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. 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.

A prospective evaluation of the use of emergency department computed tomography for suspected acute appendicitis.

Computed tomography (CT) is used increasingly to evaluate suspected cases of acute appendicitis (AA) in the emergency department (ED). This prospective study was performed to test the hypothesis that the evaluation of AA by CT in the ED remains suboptimal and that erroneous interpretation diminishes its utility. Consecutive patients 18 years of age or older were enrolled prospectively if AA was among the first three differential diagnoses listed in the record of patients undergoing evaluation of abdominal pain in the ED. Imaging of the abdomen and pelvis was obtained at the discretion of the ED staff or consultant surgeon. Initial CT interpretation was by a radiology resident or fellow along with the surgical staff, but final review by an attending radiologist occurred later. Age, gender, presenting symptoms, white blood cell (WBC) count, final CT results, and final pathology (for patients undergoing operation) were recorded. X +/- SEM, p < 0.05 by chi(2), ANOVA, or MANOVA was used for statistical analysis as appropriate. A CT scan was performed in 104 patients (83% of those meeting entry criteria), 35 of whom were male (mean age, 37 +/- 2 years) and 69 of whom were female (mean age, 39 +/- 3 years). Thirty-five patients had pathologically proved appendicitis, 28 of whom were diagnosed prospectively by CT. There were seven false-negative scans. Sensitivity, specificity, and positive predictive value for the initial CT reading were 80%, 91%, and 82%, respectively. Gender (p < 0.03), WBC count (p < 0.0002), and a positive initial CT reading (p < 0.0001) correlated with operative management. However, although final CT interpretation did correlate with pathologic confirmation of AA (p < 0.0001), initial CT interpretation did not correlate with the presence of AA (p = 0.52). The ability of CT to predict AA is dependent on the interpretative skill of the individual interpreting the images. Widespread use of CT in the evaluation of patients for AA should be implemented with caution until institution-specific protocols are validated.

A false-negative hepatobiliary scan due to the infected fundal end of a septated gallbladder.

A false-negative hepatobiliary scan due to the infected fundal end of a septated gallbladder.

Feedback: Computed tomography for subarachnoid hemorrhage

Feedback: Computed tomography for subarachnoid hemorrhage

Imaging infection with LeuTech.

LeuTech is a 99Tcm labelled, anti-CD15, IgM, murine monoclonal antibody shown to have high affinity (Kd = 10(-11) M) for CD15 receptors (5.1 x 10(5)/cell) expressed on human neutrophils. LeuTech was injected directly, intravenously, and its efficacy in imaging infection in 46 consecutive patients was determined. Human anti-mouse antibody (HAMA) response was examined in 30 normal volunteers using a standard LeuTech dose reconstituted with decayed 99Tcm solution. There were 38 true positive, six true negative, and two false negative scans. Of the 38 positive images, 33 (92%) were positive within 10 min after injection of LeuTech. LeuTech accuracy in this group of patients was 96%, sensitivity 95%, specificity 100%, positive predictive value (PPV) 100%, and negative predictive value (NPV) 75%. No elevation of the HAMA titre was observed in any of the 30 normal volunteers and no adverse reaction was noted in any patient. LeuTech is a highly promising agent for rapid imaging of infectious foci.

Positron Emission Tomography With [18F]Fluoro–2–Deoxy–D–Glucose for Diagnosis and Staging of Bile Duct Cancer

Malignant tumors with high glucose metabolic rates accumulate [18F]-fluorodeoxyglucose (FDG), a positron emitting tracer. The aim of this study was to evaluate FDG positron emission tomography (PET) for detection and staging of human cholangiocarcinoma (CC). Patients with adenocarcinoma of the biliary tree (n = 26), with benign lesions of the bile ducts (n = 8), and 20 control patients underwent FDG-PET (370 MBq [18F]-FDG, Siemens ECAT EXACT HR(+)). In a blinded fashion, 4 independent experts evaluated the PET scans visually and semiquantitatively using the standardized uptake value and a tumor/non-tumor ratio. All adenocarcinomas and benign lesions (sclerosing cholangitis, bile duct adenoma, Caroli's disease) were histologically proven and imaged by magnetic resonance imaging and endoscopic retrograde cholangioscopy. True-positive PET scans were obtained in 24 of 26 CC and false-negative scans in the other 2 (sensitivity 92.3%). The PET scan was true-negative in 18 of 20 controls and in all 8 benign biliary lesions (specificity 92.9%). Visual and semiquantitative evaluation using tumor/non-tumor ratios were equally accurate (accuracy 92.6%) whereas evaluation by standardized uptake value revealed lower accuracy (P <.05). Regional or hepatoduodenal lymph node metastases were detected with PET in only 2 of 15 cases whereas distant metastases (peritoneal carcinomatosis, pulmonary metastases) were diagnosed in 7 of 10 cases. In conclusion, PET is highly sensitive and specific for the detection and localization of CC. It can be helpful for diagnosis of distant metastases but is not suitable for detection of regional lymph node metastases.

FDG-PET for detection of pulmonary metastases from malignant primary bone tumors: Comparison with spiral CT

The purpose was the comparison of positron emission tomography using F-18-fluorodeoxy-glucose (FDG-PET) and spiral thoracic CT to detect pulmonary metastases from malignant primary osseous tumors. In 71 patients with histologically confirmed malignant primary bone tumors (32 osteosarcomas, 39 Ewing's sarcomas) 111 FDG-PET examinations were evaluated with regard to pulmonary/pleural metastases in comparison with spiral thoracic CT. Reference methods were the clinical follow-ups for 6-64 months (median 20 months) or a histopathologic analysis. In 16 patients (23%) reference methods revealed a pulmonary/pleural metastatic disease. FDG-PET had a sensitivity of 0.50, a specificity of 0.98, and an accuracy of 0.87 on a patient based analysis. Comparable values for spiral CT were 0.75, 1.00, and 0.94. It was shown that no patient who had a true positive FDG-PET had a false negative CT scan, nor was a pulmonary metastases detected earlier by FDG-PET than by spiral CT. There seems to be a superiority of spiral CT in the detection of pulmonary metastases from malignant primary bone tumors as compared with FDG-PET. Therefore, at present a negative FDG-PET cannot be recommended to exclude lung metastases. However, as specificity of FDG-PET is high, a positive FDG-PET result can be used to confirm abnormalities seen on thoracic CT scans as metastatic.

Invited commentary

Invited commentary

Evaluation of suspected appendicitis in children and young adults: helical CT.

To evaluate the accuracy of helical computed tomography (CT) for the diagnosis of appendicitis in children and to assess the utility of CT in establishing alternative diagnoses. The medical records of 154 children (median age, 12 years; age range, 1-20 years) who were suspected to have appendicitis and who underwent CT were reviewed. The gastrointestinal tract was opacified in 151 of 154 patients: Only orally administered contrast material was used in 126 patients; only rectally administered contrast material, in 21 patients; and both oral and rectal contrast material, in four patients. CT findings were correlated with surgical and histopathologic findings or with clinical follow-up findings. Sixty-four CT scans were interpreted as positive for appendicitis and included 58 true-positive and six false-positive scans. Ninety scans were interpreted as negative and included 87 true-negative and three false-negative scans. CT had a sensitivity of 95% and a specificity of 94% for the diagnosis of appendicitis. In addition, in 32 (34%) of 93 patients without appendicitis, an alternative diagnosis was established on the basis of CT findings. Helical CT is useful in a pediatric population to diagnose or exclude appendicitis and to establish an alternative diagnosis.

1. Positron Emission Tomography of Thoracic Malignancies: Reduction of Myocardial Fluorodeoxyglucose Uptake Artifacts With a Carbohydrate Restricted Diet

Purpose: To reduce the artifact caused by cardiac uptake of F-18 fluorodeoxyglucose (FDG); we investigated the change in myocardial FDG uptake after placing a group of patients on a carbohydrate-restricted diet.Methods: Case control study involving 130 whole body FDG PET scans. 73 scans were of patients on carbohydrate-restriction; the remaining 57 were without dietary restrictions. Dietary intake for the last meal prior to scanning was recorded for both groups. Coronal and axial images were assessed and scored based on myocardial FDG uptake the presence of associated image artifacts.Results: Of the 73 patients on the diet, 50 did not consume carbohydrates, while of the 57 patients without dietary restriction, 13 did not consume carbohydrates. Of the 67 patients from both groups who consumed carbohydrates prior to their PET scan, 17 (25.4%) had a clinically significant image artifact versus only 6 (9.5%) of the 63 patients who did not consume carbohydrates (P = 0.018) in their meals prior to scanning. The odds ratio was calculated to be 3.23 (confidence interval 1.09–10.00), indicating that the risk a clinically significant image artifact will occur is 3.23 times higher for patients who consume carbohydrates in their last meal prior to scanning.Conclusion: A substantial reduction in the prevalence of myocardial FDG uptake image artifacts among patients who did not consume carbohydrates was observed. A carbohydrate dietary restriction prior to scanning may play a significant role in increasing lesion detectability and in preventing false negative scans when imaging for thoracic neoplasm.

The role of computed tomographic scanning in diagnosing mediastinal node involvement in non–small cell lung cancer

Objectives: The reliability of computed tomographic scanning in evaluating mediastinal node involvement is controversial because of the high false result rate. We attempted to identify significant factors responsible for false-positive and false-negative scans. Methods: From August 1992 through April 1997, 401 patients with lung cancer who underwent major lung resection and systematic lymph node dissection were enrolled in this study. We retrospectively examined mediastinal node size, tumor location, maximum tumor dimension, the presence or absence of obstructive pneumonia, atelectasis, pulmonary fibrosis, and lymph node calcification on contrast-enhanced computed tomographic scans. We identified clinical and radiologic factors responsible for the false results by using univariate and multivariable analysis. Results: Central tumor location proved to be a significant factor of false-positive scans. Elevated carcinoembryonic antigen level and larger tumor dimension were significant factors of false-negative scans. In patients with a peripheral tumor smaller than 40 mm and normal levels of serum carcinoembryonic antigen, sensitivity, specificity, positive predictive value, and negative predictive value were 6%, 93%, 8%, and 90%, respectively. The reliability of computed tomographic scanning in this low-risk subgroup was high in detecting N0-1 disease but low in diagnosing N2 disease. Conclusion: It is not possible to accurately diagnose N2 disease by using lymph node size on computed tomographic scanning alone, especially in patients with a central tumor, an elevated serum carcinoembryonic antigen level, or a tumor of 40 mm or larger. A preoperative invasive staging procedure is indicated in these populations and may not be indicated in the population with normal computed tomographic scan results without any of these risk factors. (J Thorac Cardiovasc Surg 2000;119:1135-40)

Technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy in the differential diagnosis of cerebral abscesses.

The diagnosis of brain abscess is often difficult, as the clinical symptoms are not specific. Computed tomography (CT) and magnetic resonance imaging (MRI) are highly sensitive, but different cerebral lesions, especially neoplasms, can have the same ring-like contrast enhancement. Brain abscess is a severe illness requiring rapid diagnosis to choose the most appropriate therapy. Technetium-99m hexamethylpropylene amine oxime (HMPAO)-labelled leucocyte scintigraphy is commonly used to detect an inflammatory process. The aim of this study was to present the results obtained with leucocyte scintigraphy in 65 patients with intracranial mass lesions and clinical findings compatible to or suggestive of brain abscess. The final diagnosis, based on surgery, clinical findings and stereotatic puncture, was brain abscess in 17 patients, primary brain neoplasm in 22, brain metastasis in 16, lymphoma in 2, cysticercosis in 2, hematoma in 2 and cerebral infarction in 4. 99mTc-HMPAO leucocyte scintigraphy was positive in all abscess cases. The scan was negative in the rest of the patients examined, with the exception of one lesion, which was finally diagnosed as a tumour (1 false-positive). All patients who did not have false-negative scans were treated with steroids. The sensitivity, specificity and diagnostic accuracy of leucocyte scintigraphy was 100%, 97.8% and 98.4%, respectively. In conclusion, in our experience, leucocyte scintigraphy is a valuable aid in the differential diagnosis between abscess and neoplasm.

123I‐METAIODOBENZYLGUANIDINE SCANS IN PHAEOCHROMOCYTOMA DIAGNOSIS: CURRENT CLINICAL PRACTICE AND RELATIONSHIP TO BIOCHEMICAL SCREENING

SUMMARYThe use in practice of 123I‐metaiodobenzylguanidine (MIBG) scans in phaeochromocytoma diagnosis in a teaching hospital over an eight‐year period is reported. MIBG scans were performed in 43 patients and the clinical context is reviewed and reported in 42 of these. A paraganglioma and five phaeochromocytomas were found in the MIBG series. There were no false negative MIBG scans. CT was performed in 61.9%, abdominal ultrasound in 45.3% and MRI in 7.1% of the patients. Urinary catecholamines and metanephrines are considered the best screening tests for phaeochromocytoma and false positive biochemistry values were associated with MIBG scans in 35% of the cases. Despite published limitations on its sensitivity, MIBG scans were the only modality used in 21.4%; 25% of the scans were performed for clinical reasons when the biochemical screen was within the reference range. MIBG is superior to CT and MRI for the localisation of suspected recurrence after surgery and is also useful for the detection of extra adrenal tumours and metastases.

Technetium-99m Sestamibi Scintigraphy and Bone Densitometry in Primary Hyperparathyroidism

To review our recent experience with technetium-99m sestamibi scintigraphy in identification and localization of parathyroid adenomas and to determine bone mineral loss associated with primary hyperparathyroidism. Thirty-two double-phase technetium-99m sestamibi scans were obtained in 26 patients (22 female and 4 male patients; age range, 14 to 78 years). Serum calcium and intact parathyroid hormone concentrations were measured before scintigraphy. Histopathologic correlation was obtained in all patients who underwent a surgical procedure. Seventeen patients underwent bone densitometry studies of the lumbar spine and hip with use of dual-energy x-ray absorptiometry. Of the 32 scans, 17 (53%) were suggestive of a parathyroid adenoma ("positive"). In these patients, the mean serum calcium concentration was 2.68 mmol/L and the mean serum parathyroid hormone concentration was 669 pg/mL. Overall, one false-negative scan and one false-positive scan were encountered. The overall sensitivity for surgically proven detection and localization of parathyroid adenoma was 90%. The bone density measurements in patients with positive scans were substantially lower in the lumbar spine (mean T score, 2.9) and in the hip (mean T score, 2.1) in comparison with normal control subjects and significantly lower than in those with a negative scan (spine, P = 0.011; hip, P = 0.015). Double-phase technetium-99m sestamibi scintigraphy is highly sensitive and useful in detection and localization of parathyroid adenomas. Patients with primary hyperparathyroidism lose bone mineral from both cortical and cancellous bone sites.

The utility of technetium 99m pertechnetate scintigraphy in the evaluation of patients with Meckel's diverticulum

Purpose: The aim of this study was to assess the utility of technetium (Tc) 99m pertechnetate scintigraphy in the diagnostic workup of the pediatric patient with gastrointestinal (GI) bleeding and a suspected Meckel's diverticulum.Methods: The charts of 235 consecutive patients evaluated with a Meckel's scan (n = 165) or with the discharge diagnosis of Meckel's diverticulum (n = 70) between January 1975 and October 1997 were reviewed for presenting symptoms, bleeding characteristics, diagnostic studies and pathological diagnosis. Those patients with lower GI bleeding and a serum hemoglobin level less than 11.0 g/dL who underwent a99mTc pertechnetate scan (n = 43) were assessed for utility of the scan.Results: In all patients the Meckel's scan had a positive and negative predictive value of 0.93. However, in patients with lower GI bleeding and a hemoglobin less than 11.0 g/dL the Meckel's scan had a sensitivity of 0.60, a positive predictive value of 1.0, a specificity of 0.96, but only a negative predictive value of 0.74. As such, the probability that a child who presents with GI bleeding and a serum hemoglobin less than 11 g/dL will have a Meckel's diverticulum despite a negative Meckel's scan of 0.26. We further evaluated the eight patients with a false-negative scan: ectopic gastric mucosa was present on pathological examination in all eight patients. Pentagastrin stimulation was performed at the time of scintigraphic study in three of eight. Six of these eight patients had duplicate scans that also were negative. Patients with a false-negative (FN) scan had significantly increased hospital charges when compared with those with a true positive (TP) scan (TP = $5012 ± 1992; FN = $8554 ± 1506; P = .0001). Clinical suspicion had a major effect on the decision-making process in these patients independent of the results of the Meckel's scan, and all eight patients ultimately underwent exploratory laparoscopy-laparotomy with Meckel's diverticulectomy despite the scan results.Conclusions: The relatively low negative predictive value of the Meckel's scan may result in the need for operative evaluation despite the scan data. As such, the contribution of the scan to clinical decision making is low. These findings suggest that exploratory laparotomy or laparoscopy may be indicated instead of scintigraphic scanning in the assessment of the anemic (hemoglobin less than 11 g/dL) pediatric patient with lower GI bleeding, especially in patients in whom a high suspicion for a bleeding Meckel's diverticulum exists.

When are false-positive and false-negative 18F-FDG PET scans really false?

When are false-positive and false-negative 18F-FDG PET scans really false?

PET Scanning with 18F 2-Fluoro-2-Deoxy- d-Glucose (FDG) in Patients with Melanoma : Benefits and Limitations

We reviewed our experience with positron imaging tomography (PET) scanning from 1996–1998 in 45 patients (51 scans) with high risk ( n = 15) or recurrent melanoma ( n = 30). Positive or negative PET findings were considered correct if confirmed or refuted by other radiologic modalities or biopsy within 6 weeks, or clinical follow up within 6 months. PET scans were usually obtained to make a decision regarding surgical management (29/51 scans, 57%) or to confirm that a patient was disease free (12/51 scans, 23%). PET results facilitated clinical decision making in 15/45 (33%) patients, often due to the detection of distant disease making a surgical procedure inappropriate (5/15, 33%). There were 3 false positive (6%) and 7 false negative (14%) PET scans. False negative scans occurred in patients with small volume disease of the lung (4 patients) or CNS (2 patients, 3 scans). Three patients had false positive scans. These were secondary to benign hepatic tumors and sarcoidosis (one patient each). One patient with stage IV melanoma had PET findings not confirmed by CT scanning or clinical follow-up. PET scanning was clinically useful in a third of patients in our initial experience, and false positives were uncommon. Small volume disease in the lung or CNS may be missed by PET, and additional imaging modalities should be obtained when patient management would be impacted.

Effectiveness of positron emission tomography for the detection of melanoma metastases.

The purpose of this study was to determine the sensitivity, specificity, and clinical utility of 18F 2-fluoro-2-deoxy-D-glucose (FDG) total-body positron emission tomography (PET) scanning for the detection of metastases in patients with malignant melanoma. Recent preliminary reports suggest that PET using FDG may be more sensitive and specific for detection of metastatic melanoma than standard radiologic imaging studies using computed tomography (CT). PET technology is showing utility in the detection of metastatic tumors from multiple primary sites including breast, lung, lymphoma, and melanoma. However, little information is available concerning the general utility, sensitivity, and specificity of PET scanning of patients with metastatic melanoma. One hundred three PET scans done on 76 nonrandomized patients having AJCC stage II to IV melanoma were prospectively evaluated. Patients were derived from two groups. Group 1 (63 patients) had PET, CT (chest and abdomen), and magnetic resonance imaging (MRI; brain) scans as a part of staging requirements for immunotherapy protocols. Group 2 (13 nonprotocol patients) had PET, CT, and MRI scans as in group 1, but for clinical evaluation only. PET scans were done using 12 to 20 mCi of FDG given intravenously. Results of PET scans were compared to CT scans and biopsy or cytology results. PET scanning for the detection of melanoma metastases had a sensitivity of 94.2% and a specificity of 83.3% compared to 55.3% and 84.4%, respectively, for CT scanning. Factors that produced false-positive PET scans were papillary carcinoma of the thyroid (1), bronchogenic carcinoma (1), inflamed epidermal cyst (1), Warthin's tumor of the parotid gland (1), surgical wound inflammation (2), leiomyoma of the uterus (1), suture granuloma (1), and endometriosis (1). The four false-negative scans were thought to be due to smaller (<0.3 to 0.5 cm) and diffuse areas of melanoma without a mass effect. PET scanning is extremely sensitive (94.2%) and very specific (83.3%) for identifying metastatic melanoma, particularly in soft tissues, lymph nodes, and the liver. A number of second primary or metastatic tumors and an inflammatory response can also be localized by PET. This observation mandates a close clinical correlation with positive PET and emphasizes the importance of establishing a tissue diagnosis. False-negative scans in the presence of metastases are rare (4% of scans). Metastases < or =5 mm in diameter may not image well. PET is superior to CT in detecting melanoma metastases and has a role as a primary strategy in the staging of melanoma.