ROC study and SUV threshold using quantitative multi-modal SPECT for bone imaging.

BACKGROUND: We investigated the clinical performance of a quantitative multi-modal SPECT/CT reconstruction platform for yielding radioactivity concentrations of bone imaging with 99mTc-methylene diphosphonate (MDP) or 99mTc-dicarboxypropane diphosphonate (DPD). The novel reconstruction incorporates CT-derived tissue information while preserving the delineation of tissue boundaries. We assessed image-based reader concordance and confidence, and determined lesion classification and SUV thresholds from ROC analysis. METHODS: Seventy-two cancer patients were scanned at three US and two German clinical sites, each contributing two experienced board-certified nuclear medicine physicians as readers. We compared four variants of the reconstructed data resulting from the Flash3D (F3D) and the xSPECT Bone™ (xB) iterative reconstruction methods and presented images to the readers with and without a fused CT, resulting in four combinations. We used an all-or-none approach for inclusion, compiling results only when a reader completed all reads in a subset. After the final read, we conducted a "surrogate truth" reading, presenting all data to each reader. For any remaining discordant lesions, we conducted a consensus read. We next undertook ROC analysis to determine SUV thresholds for differentiating benign and lesional uptake. RESULTS: On a five-point rating scale of image quality, xB was deemed better by almost two points in resolution and one point better in overall acceptance compared to F3D. The absolute agreement of the rendered decision between the nine readers was significantly higher with CT information either inside the reconstruction (xB, xBCT) or simply through image fusion (F3DCT): 0.70 (xBCT), 0.67 (F3DCT), 0.64 (xB), and 0.46 (F3D). The confidence level to characterize the lesion was significantly higher (3.03x w/o CT, 1.32x w/CT) for xB than for F3D. There was high correlation between xB and F3D scores for lesion detection and classification, but lesion detection confidence was 41% higher w/o CT, and 21% higher w/CT for xB compared to F3D. Without CT, xB had 6.6% higher sensitivity, 7.1% higher specificity, and 6.9% greater AUC compared to F3D, and similarly with CT-fusion. The overall SUV-criterion (SUVc) of xB (12) exceeded that for xSPECT Quant™ (xQ; 9), an approach not using the tissue delineation of xB. SUV critical numbers depended on lesion volume and location. For non-joint lesions > 6 ml, the AUC for xQ and xB was 94%, with SUVc > 9.28 (xQ) or > 9.68 (xB); for non-joint lesions ≤ 6 ml, AUCs were 81% (xQ) and 88% (xB), and SUVc > 8.2 (xQ) or > 9.1 (xB). For joint lesions, the AUC was 80% (xQ) and 83% (xB), with SUVc > 8.61 (xQ) or > 13.4 (xB). CONCLUSION: The incorporation of high-resolution CT-based tissue delineation in SPECT reconstruction (xSPECT Bone) provides better resolution and detects smaller lesions (6 ml), and the CT component facilitates lesion characterization. Our approach increases confidence, concordance, and accuracy for readers with a wide range of experience. The xB method retained high reading accuracy, despite the unfamiliar image presentation, having greatest impact for smaller lesions, and better localization of foci relative to bone anatomy. The quantitative assessment yielded an SUV-threshold for sensitively distinguishing benign and malignant lesions. Ongoing efforts shall establish clinically usable protocols and SUV thresholds for decision-making based on quantitative SPECT.

Redistribution of visceral blood volume in upright exercise in healthy volunteers.

Exercise induced changes in the blood volume of visceral organs (cardiopulmonary and liver, spleen, and kidneys) were determined by scintillation camera imaging of the distribution of technetium-99m-labeled red blood cells in the thorax and abdomen of ten healthy adult volunteers. Graded upright bicycle exercise was performed to the point of exhaustion with the volunteer positioned with his/her back to the scintillation camera and data recording was synchronized to the pedal cycle to minimize patient motion artifacts within the data. The first image from each level of exercise was analyzed by placing regions of interest over the spleen, liver, kidneys, and right lung. The counts in each organ were expressed as a percent of activity at zero workload. Analysis of data using Hotelling's t-squared analysis to see if overall differences existed between the last four measurements (up to the time of exhaustion) regarding percent change from baseline for spleen, kidney, liver, and right lung were made. The splanchnic bed had a significant decrease in blood volume. The spleen decreased 39%, while the liver decreased 14%. For the kidney and liver, no significant differences were achieved (p greater than 0.24, p less than 0.15, respectively). The lung increased its blood volume to 128% of control, significant with p less than 0.02. This data demonstrates that in healthy volunteers there is normal redistribution of blood volume during maximal exercise with a significant reduction in blood volume of the spleen as well as a significant rise in blood volume within the lungs.

A modified method for the in vivo labeling of red blood cells with Tc-99m: concise communication.

The rate of incorporation of Tc-99m into red blood cells pretinned in vivo was measured by collecting blood samples in stannous DTPA solution, which served as a competing ligand for Tc-99m. This collection technique permitted a measurement of high-affinity red-cell labeling efficiency at the instant of sampling. At 0.5 min after injection only 62% of technetium is tightly bound to the red cell; this rises to 94.5% at 10 min. Based on the graded labeling of the red cells, the in vivo labeling procedure was modified by isolating pertechnetate and red blood cells tinned in vivo in a syringe during the first 10 min of labeling. The pertechnetate is thus prevented from distributing to extravascular compartments, and 90% of the injected Tc-99m is firmly bound to red blood cells at the time of injection. In a series of 23 patients, seven were tested with the in vivo method and seven with the modified in vivo method, and nine patients were tested with each method on separate occasions. A decrease in gastric activity and improved image quality were found with the modified method compared with the standard method of in vivo red-cell labeling.

Ventilation-perfusion scintigraphy in the PIOPED study. Part I. Data collection and tabulation.

The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study of more than 700 patients is the largest existing study of the accuracy of lung scintigraphy in the diagnosis of acute pulmonary embolism. Perfusion scans were obtained in all patients and ventilation scans in almost all, using standardized techniques. Chest radiographs were obtained in all patients within 12 hr of the lung scan. Most patients underwent pulmonary arteriography. The images were interpreted according to a set of interpretive criteria which remained constant throughout the trial. A standardized, detailed description of each image set was derived by consensus of teams of two readers blinded to clinical and arteriographic findings. This communication reports the methods used to describe and categorize the ventilation-perfusion scintigrams obtained in patients who were enrolled in the PIOPED study. Scintigraphic technique is reviewed briefly, probability assessment is described and the scan description is reviewed in detail. The form used to describe the findings on ventilation-perfusion scans is reproduced. Use of this standardized description permits retrospective evaluation of the PIOPED interpretive criteria. In addition, it represents a rigorous approach to scan analysis which could facilitate application of formal interpretive schemes and enhance the reproducibility of lung scan interpretations in the clinical setting.

Ventilation-perfusion scintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations.

This article presents an evaluation of the criteria used for categorical interpretation of the ventilation-perfusion (V/Q) scans performed in the PIOPED study. In addition, the correlation of percent probability estimates with the actual frequency of pulmonary embolism (PE) is presented. Cases which met the PIOPED criteria for various diagnostic categories were selected by computerized search of the detailed scan descriptions that had been done as part of the study. The process by which the scans were described was detailed in Part I of this report. Most of the criteria appropriately categorized V/Q scans which satisfied them. However, we recommend that three criteria should be reconsidered: 1. A single moderate perfusion defect is appropriately categorized as intermediate, rather than as low probability. 2. Extensive matched V/Q abnormalities are appropriate for low probability, provided that the chest radiograph is clear. On the other hand, single-matched defects may be better categorized as intermediate probability. Although due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. 3. Two segmental mismatches may not be the optimum threshold for high probability, and in some cases should be considered for intermediate probability. However, due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. We suggest that the revised criteria resulting from these adjustments should now be used for the interpretation of V/Q scans.

Hemodynamic, pharmacokinetic and clinical response to CI-930 in congestive heart failure due to ischemic or dilated cardiomyopathy.

CI-930, a new type III phosphodiesterase inhibitor, was evaluated for treatment of refractory congestive heart failure. The hemodynamic, pharmacokinetic and clinical response to the drug was determined in 10 patients. At the peak plasma concentration after intravenous CI-930, cardiac index increased from 2.0 to 2.7 liters/min/m2 (p less than 0.002), pulmonary artery wedge pressure decreased from 26 to 17 mm Hg (p less than 0.001) and systemic vascular resistance decreased from 1,999 to 1,471 dynes cm-5 (p less than 0.05). Heart rate and blood pressure did not change significantly. Similar changes were observed with oral CI-930. Peak CI-930 plasma concentration occurred 1.2 +/- 0.8 hours after oral administration. Beneficial hemodynamic effects were sustained 12 to 18 hours after the oral dose. The sustained hemodynamic effects observed after oral administration appear to be related to an active metabolite of CI-930 that has prolonged duration of action and slow washout. The drug was well tolerated and has potential for treatment of congestive heart failure.

The role of indium-111 white blood cells in inflammatory bowel disease.

Inflammatory bowel disease in patients may be difficult to diagnose because of the complex problems associated with this disease. Radionuclides are able to provide a rapid and effective method of imaging the bowel in patients with active inflammatory bowel disease. In the past, clinical work-ups have included barium x-ray studies and endoscopy. Scarring and fistula formation have made it difficult to determine between the active disease and abscesses that may occur. Gallium-67 (67Ga) has been very useful in imaging patients with inflammatory bowel disease, but the multiple-day imaging procedure has been a limitation for the clinicians when achieving a diagnosis. Recent results with Indium-111 (111In)--labeled WBCs have provided excellent correlation between clinical symptoms and colonoscopy findings in patients with inflammatory bowel disease. This technique has also allowed the differentiation between reoccurring inflammatory bowel disease and abscesses that accompany the disease within a 24-hour time period. The use of intravenous (IV) glucagon has increased the clarity of the images in the small bowel. Technetium 99m (99mTc) diethylenetriaminepentaacetic acid (DTPA) has been used in patients with inflammatory bowel disease demonstrating promising results. Investigators feel labelling 99mTc with WBCs will be improved, therefore yielding a greater efficiency, which will have a major impact on imaging patients with inflammatory bowel disease. Imaging patients with inflammatory bowel disease using radionuclides has yielded promising results. This is a significant advancement over barium radiography and endoscopy exams.

Imaging of inflammatory processes with labeled cells.

Radionuclide techniques for localizing inflammatory processes had relied heavily upon 67Ga-citrate until McAfee and Thakur described the technique for the radiolabeling of leukocytes with 111In-oxine. Since their initial description in 1976 there has been continued development of the radiopharmaceutical, as well as clinical efficacy. At present 111In-labeled leukocytes continue to be handled as an investigational new drug but this has not greatly limited its clinical availability. Indium-111 leukocytes are the agent of choice for evaluation of patients with fever of unknown origin, osteomyelitis, and prosthetic graft infections; and preliminary data shows great promise in the area of detecting reoccurrence of inflammatory bowel disease. This article attempts to review currently accepted uses of 111In leukocytes as well as potential areas of application.

Detection of gastrointestinal bleeding with 99mTc-labeled red blood cells.

Using a modified in vivo Tc-99M red cell labeling technique, gastrointestinal bleeding scintigraphy was performed in 100 patients with GI bleeding. Sixty-two patients with melena or bright red blood per rectum had positive scintiscans. In comparison to results of angiography, endoscopy, surgery and contrast radiography, radionuclide scintigraphy correctly located the site of bleeding in 83% of patients. The procedures could be performed over a 24 hr period which increased the sensitivity of the test since 85% of the scintiscans were positive at one hr or greater after the onset of imaging. The procedure was more sensitive than angiography in detecting sources of GI bleeding. We conclude that GI bleeding scintigraphy 99mTc-red cells in an accurate and effective method to detect upper and lower GI bleeding in patients with acute intermittent gastrointestinal bleeding.

Treatment of massive acute pulmonary embolism. The use of low doses of intrapulmonary arterial streptokinase combined with full doses of systemic heparin.

The efficacy of low-dose, locally administered streptokinase (SK) combined with full therapeutic systemic doses of heparin was investigated. Seven patients with angiographically proven massive acute pulmonary embolism were treated. Streptokinase, 10,000-20,000 units/hour, was administered directly into the left or right pulmonary artery for 9 to 24 hours. Heparin was administered concurrently. The number of unperfused segments of the infused lung shown on the lung scan decreased from 5 +/- 2 to 2 +/- 1 after 12-24 hours (p less than .01). No change was shown in the contralateral lung. The angiographic index of severity score in the infused lung decreased from 16 +/- 1 to 9 +/- 4 (p less than .01). The partial pressure of oxygen in arterial blood improved within four hours. In spite of the low doses of streptokinase, however, two major bleeding episodes occurred that required blood transfusion. In conclusion, low dose intrapulmonary streptokinase, combined with intravenous heparin, may provide a therapeutic option in patients with life-threatening massive acute pulmonary embolism in whom full dose lytic therapy may be hazardous, although even low dose lytic therapy was associated with risk.

Localization of residual medullary thyroid cancer by thallium/technetium scintigraphy.

Whole-body thallium/technetium subtraction scintiscans, with thallium 201 chloride and technetium 99m pertechnetate, were obtained on 10 patients with medullary thyroid cancer with postoperative elevations of serum calcitonin values. Seven patients had the hereditary variant of medullary thyroid cancer (the multiple endocrine neoplasia, type II syndrome) while three patients had the sporadic form. Negative scans were obtained on five patients with basal calcitonin levels less than 3 ng/ml (normal less than 0.35 ng/ml). Five other patients with elevated calcitonin levels (range 3.6 to 69.2 ng/ml; mean 28.3 ng/ml) had positive scans that have guided further surgical approaches. Serum calcitonin appears to remain the most sensitive indicator of residual medullary thyroid cancer while localization of this residual tumor tissue frequently can be obtained through thallium/technetium subtraction imaging in both the hereditary and sporadic forms of the disease.

Nuclear medicine imaging of inflammatory bowel disease.

With the availability of indium-labeled white blood cells, radionuclide imaging studies have a definite role in the diagnosis and staging of patients with inflammatory bowel disease. The In-111 white blood cell study is particularly helpful in evaluating recurrent disease in patients with severe intercurrent diseases and in screening patients without the need for barium examinations.

MR imaging strategies in primary and metastatic malignancy.

This article gives the rationale of the indications for the use of MRI in the evaluation of primary and metastatic malignancies of the neck, chest, abdomen, male and female pelvis, and musculoskeletal system. The imaging protocols for each of these areas is also included.

The "false-negative" Meckel's scan.

A case is presented of a 17-month-old girl who underwent two Meckel's scans with Tc-99m pertechnetate. The initial study was interpreted as normal while a subsequent study five days later was definitely positive. Surgery immediately following the positive Meckel's scan demonstrated a Meckel's diverticulum containing gastric mucosa without evidence of active hemorrhage. This prompted a review of the literature in reference to false-negative Meckel's scans which revealed a wide variance in the reported incidence of false-negative examinations. Repeat scintigraphy in the face of a strong clinical suspicion after an initial normal study may decrease the indicence of false-negative imaging series.

Evaluation of scrotal edema in a patient on peritoneal dialysis. A case report.

A 50-year-old man placed on peritoneal dialysis for end stage renal disease developed unilateral (left) scrotal edema following infusion of dialysis fluid into the peritoneum. The left side of the scrotum and left inguinal canal were surgically explored and a left hydrocele was removed. Following surgery, the patient again demonstrated left scrotal edema during peritoneal dialysis. Tc-99m MAA (5.0 mCi, 185 mBq) was injected into a 2-liter bag of dialysis fluid, which was subsequently infused into the peritoneum. The communication between the peritoneal cavity and the left inguinal canal was demonstrated.

Delayed rupture of the spleen. A case report.

The diagnosis of delayed rupture of the spleen is demonstrated and discussed by presenting a case in which the patient had significant thoracoabdominal trauma with an initially normal liver/spleen scintigram and benign hospital course. Twenty-three days after the trauma, the patient developed an acute abdominal crisis that brought him to the emergency room where an emergency ultrasound revealed hemoperitoneum and a subcapsular hematoma. At laparotomy, a splenic rupture was found. A splenectomy was not performed. Postoperative liver/spleen scintigram showed a persistent defect which was not present on the initial liver/spleen scintigram.

Abnormal pelvic venous collaterals demonstrated during a gastrointestinal bleeding study.

A Tc-99m blood cell study, performed on a patient with suspected gastrointestinal bleeding, demonstrated an unusual configuration of pelvic venous collaterals associated with idiopathic iliac vein occlusion. The cause of these findings subsequently was confirmed by intravenous digital subtraction angiography. This case demonstrates the importance of the dynamic phase of gastrointestinal bleeding studies in correctly identifying vascular abnormalities.

Detection of hemangiomas using whole-body imaging with technetium-99m labeled RBCs.

Hemangiomas are easily, quickly and relatively noninvasively detected using whole-body imaging with Tc-99m labeled RBCs. A case in which this method was used to confirm known lesions and detect additional unsuspected lesions is described. This method can also be useful in the detection and evaluation of other types of vascular malformations, such as arteriovenous communications. The lesions must be of sufficient size and flow to be seen. Applications include the examination of patients known to have one vascular malformation in a search for additional lesions and the screening of relatives of patients with familial conditions that include hemangiomas.

Magnetic Resonance Imaging for Meniscal Tears of the Knee.

In brief: Magnetic resonance imaging (MRI). has become a standard diagnostic technique in many medical facilities for evaluating the menisci of the knee. MRI provides superior soft-tissue contrast with high resolution and takes little time (typically less than 30 minutes). It does not require intra-articular contrast media and is not limited to surface abnormalities, as are arthrography and arthroscopy. Unlike MRI, both arthrography and arthroscopy cause disturbances to the external capsule of the knee, with associated patient discomfort and limited physical activity for some time following the procedure. The author discusses the advantages of MRI and presents a case report in which it was used to make the diagnosis and determine the appropriate treatment modality.