Twyla Bartel

F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma

F18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a powerful tool to investigate the role of tumor metabolic activity and its suppression by therapy for cancer survival. As part of Total Therapy 3 for newly diagnosed multiple myeloma, metastatic bone survey, magnetic resonance imaging, and FDG-PET scanning were evaluated in 239 untreated patients. All 3 imaging techniques showed correlations with prognostically relevant baseline parameters: the number of focal lesions (FLs), especially when FDG-avid by PET-computed tomography, was positively linked to high levels of beta-2-microglobulin, C-reactive protein, and lactate dehydrogenase; among gene expression profiling parameters, high-risk and proliferation-related parameters were positively and low-bone-disease molecular subtype inversely correlated with FL. The presence of more than 3 FDG-avid FLs, related to fundamental features of myeloma biology and genomics, was the leading independent parameter associated with inferior overall and event-free survival. Complete FDG suppression in FL before first transplantation conferred significantly better outcomes and was only opposed by gene expression profiling-defined high-risk status, which together accounted for approximately 50% of survival variability (R(2) test). Our results provide a rationale for testing the hypothesis that myeloma survival can be improved by altering treatment in patients in whom FDG suppression cannot be achieved after induction therapy.

Repetitive Transcranial Magnetic Stimulation for Tinnitus: A Case Study

Objectives/Hypothesis: Correlate subjective improvements in tinnitus severity with restoration of cortical symmetry and sustained attention after neuronavigated low‐frequency, repetitive transcranial magnetic stimulation (rTMS).

Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3

Prognostic implications of 3 imaging tools, metastatic bone survey, magnetic resonance imaging, and positron emission tomography (PET), were evaluated in 2 consecutive Total Therapy 3 trials for newly diagnosed myeloma. Data including PET at baseline and on day 7 of induction as well as standard prognostic factors were available in 302 patients of whom 277 also had gene expression profiling (GEP)-derived risk information. According to multivariate analysis, more than 3 focal lesions on day 7 imparted inferior overall survival and progression-free survival, overall and in the subset with GEP-risk data. GEP high-risk designation retained independent significance for all 3 end points examined. Thus, the presence of > 3 focal lesions on day 7 PET follow-up may be exploited toward early therapy change, especially for the 15% of patients with GEP-defined high-risk disease with a median overall survival expectation of 2 years. This trial was registered at www.clinicaltrials.gov as #NCT00081939 and # NCT00572169.

Imaging of Multiple Myeloma and Related Plasma Cell Dyscrasias

Multiple myeloma (MM) is an incurable plasma cell malignancy of the bone marrow. MM has 3 components: diffuse marrow infiltration, focal bone lesions, and soft-tissue (extramedullary) disease. The hallmark biomarker in blood or urine is a monoclonal immunoglobulin, the monoclonal protein. Waldenstrom macroglobulinemia is a similar disease with secretion of IgM. Staging is classically performed with the 1975 Durie–Salmon system, which includes conventional radiographs. Recently updated, the Durie–Salmon Plus staging system includes CT, MRI, and 18F-FDG PET/CT. The hallmark radiographic lesion of symptomatic MM is a well-demarcated, focal osteolytic bone lesion. The number of focal bone lesions correlates inversely with outcome. Extramedullary disease is typically an aggressive, poorly differentiated form of MM that confers inferior outcome, with median survival of less than 1 y if present at diagnosis. Achievement of a complete response on 18F-FDG PET before stem-cell transplantation correlates with a superior outcome.

Standard and novel imaging methods for multiple myeloma: correlates with prognostic laboratory variables including gene expression profiling data

Multiple myeloma causes major morbidity resulting from osteolytic lesions that can be detected by metastatic bone surveys. Magnetic resonance imaging and positron emission tomography can detect bone marrow focal lesions long before development of osteolytic lesions. Using data from patients enrolled in Total Therapy 3 for newly diagnosed myeloma (n=303), we analyzed associations of these imaging techniques with baseline standard laboratory variables assessed before initiating treatment. Of 270 patients with complete imaging data, 245 also had gene expression profiling data. Osteolytic lesions detected on metastatic bone surveys correlated with focal lesions detected by magnetic resonance imaging and positron emission tomography, although, in two-way comparisons, focal lesion counts based on both magnetic resonance imaging and positron emission tomography tended to be greater than those based on metastatic bone survey. Higher numbers of focal lesions detected by magnetic resonance imaging and positron emission tomography were positively linked to high serum concentrations of C-reactive protein, gene-expression-profiling–defined high risk, and the proliferation molecular subgroup. Positron emission tomography focal lesion maximum standardized unit values were significantly correlated with gene-expression-profiling–defined high risk and higher numbers of focal lesions detected by positron emission tomography. Interestingly, four genes associated with high-risk disease (related to cell cycle and metabolism) were linked to counts of focal lesions detected by magnetic resonance imaging and positron emission tomography. Collectively, our results demonstrate significant associations of all three imaging techniques with tumor burden and, especially, disease aggressiveness captured by gene-expression-profiling–risk designation. (Clinicaltrials.gov identifier: NCT00081939)

Single photon emission computed tomography (SPECT) should be routinely performed for the detection of parathyroid abnormalities utilizing technetium-99m sestamibi parathyroid scintigraphy.

Rationale: The current procedure guideline for performing dual-phase (DP) parathyroid scintigraphy, using technetium-99m sestamibi (Tc-99m MIBI) does not mandate the use of single photon emission computed tomography (SPECT) imaging for the detection of parathyroid adenoma (PA) or hyperplasia (PH). The aim of our study was to determine whether DP SPECT (DPS) is significantly superior to DP planar (DPP) imaging in the detection of these abnormalities, justifying its routine use with Tc-99m MIBI parathyroid scintigraphy. Methods: Thirty-six consecutive patients with biochemically-proven hyperparathyroidism who subsequently underwent surgical evaluation were studied. All patients underwent early and delayed planar and SPECT imaging at 15 and 90 minutes postinjection of 1.11 GBq (30 mCi) of Tc-99m MIBI. The sensitivity and false-positive rate of DPP and DPS Tc-99m MIBI scintigraphy were compared by retrospectively and blindly interpreting the images and comparing the results with surgical findings. Results: All 36 patients were shown to have either 1 PA (n=27), 2 PAs (n=1), or PH (n=8). Overall, 29 adenomas and 24 hyperplastic glands were found at surgery. On a per patient basis, the sensitivity for the detection of PA or PH for DPP was 42% (15/36) compared with 67% (24/36) for DPS (P = 0.03). For the detection of PAs, the sensitivity of DPP was 54% (15/28) versus 79% (22/28) for DPS (P = 0.05), whereas for the detection of PH, the sensitivities were 0% (0/8) for DPP versus 25% (2/8) for DPS (P = 0.13). There were 2 false-positive scans using DPP versus only 1 false-positive scan with DPS, resulting in false-positive rates of 7% and 4%, respectively. The combination of DPP and DPS did not add any advantage in detecting either PA or PH compared with DPS alone. Conclusions: DPS is significantly more sensitive, and at least as specific, compared with DPP in detecting parathyroid abnormalities in patients with primary hyperparathyroidism and should, therefore, be routinely used when DP Tc-99m MIBI is used in this setting. An algorithm for best utilization of this technique to determine the appropriate surgical approach in patients with primary hyperparathyroidism is presented.

Maintenance Repetitive Transcranial Magnetic Stimulation Can Inhibit the Return of Tinnitus

Objectives/Hypothesis: A single patient was tested to examine the safety and feasibility of using maintenance sessions of low‐frequency repetitive transcranial magnetic stimulation (1 Hz rTMS) to reduce tinnitus loudness and prevent its return over time.

Variable changes in PET activity before and after rTMS treatment for tinnitus

The objective was to determine whether low‐frequency repetitive transcranial magnetic stimulation (rTMS) improves tinnitus by decreasing neural activity in auditory processing regions of the temporal cortex and the utility of positron emission tomography (PET) for targeting treatment.

Can the pathology of a thyroid nodule be determined by positron emission tomography uptake

Objectives. To determine if standardized uptake values (SUV) on positron emission tomography (PET) are predictive of thyroid pathology and the significance of serial SUV measurements of thyroid nodules over time. Study Design. Case series with chart review. Setting. Academic health center. Subjects. In total, 23,384 PET and PET/computed tomography (CT) scans were performed between December 2001 and April 2011. Methods. Patients with incidental thyroid uptake were identified. SUVmax, age, sex, size of thyroid lesion, indication for PET scan, and cytology/pathology were collected. Results. Incidental thyroid uptake was noted in 1309 PET scans (5.60%), focal uptake in 690 (2.95%), and diffuse uptake in 619 (2.65%). Complete data were available for 359 PET scans from 103 patients. Malignancy was identified in 28 patients (27%). Twenty-five of the 28 lesions (89%) were primary thyroid malignancies. A significant difference between malignant SUVmax and benign SUVmax was found (mean ± SD, 7.04 ± 7.88 for malignancies vs 3.85 ± 3.06 for benign tumors, P = .0292). Receiver operating characteristics curves were constructed on patients with PET data within 3 months of diagnosis and indicated that a SUVmax of 4.2 differentiated maximally between benign and malignant lesions. Serial SUV uptake had no significant change over time. Conclusion. All thyroid nodules with focal uptake on 18F-fluorodeoxyglucose–PET/CT should be considered at higher risk of malignancy than those discovered incidentally by other imaging modalities. Higher SUVmax values are more indicative of malignant lesions. All lesions should be evaluated with ultrasonography ± fine-needle aspiration if no clinical contraindications exist. Size of the primary nodule does not influence SUVmax uptake.

A hand-held beta imaging probe for FDG

ObjectivesAdvances in radiopharmaceuticals and clinical understanding have escalated the use of intraoperative gamma probes in surgery. However, most probes on the market are non-imaging gamma probes that suffer from the lack of ancillary information of the surveyed tissue area. We have developed a novel, hand-held digital Imaging Beta Probe™ (IBP™) to be used in surgery in conjunction with beta-emitting radiopharmaceuticals such as 18FDG, 131I and 32P for real-time imaging of a surveyed area with higher spatial resolution and sensitivity and greater convenience than existing instruments.MethodsWe describe the design and validation of a hand-held beta probe intended to be used as a visual mapping device to locate and confirm excision of 18FDG-avid primary tumors and metastases in an animal model.ResultsWe have demonstrated a device which can generate beta images from 18FDG avid lesions in an animal model.ConclusionsIt is feasible to image beta irradiation in animal models of cancer given 18FDG. This technology may be applied to clinical mapping of tumors and/or their metastases in the operating room. Visual image depiction of malignancy may aid the surgeon in localization and excision of lesions of interest.