Editorial Comment: Highlighting the Opportunity for Advanced Neuroimaging in the Presurgical Evaluation of Adults With Medically Refractory EpilepsyPatrick J. Peller, MD1Audio Available | Share

AIM:report primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. METHODS:In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). RESULTS:Of 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). CONCLUSIONS:Adding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.

Lymphoscintigraphy plays a vital role in sentinel lymph node (SLN) identification in oncologic breast surgery. The effectiveness of SLN localization and the degree of patient pain were compared between filtered 99mTc-sulfur colloid (99mTc-SC) and 99mTc-tilmanocept. Methods: A retrospective review of patients undergoing lymphoscintigraphy for breast cancer using 99mTc-SC (June 1, 2010, to December 31, 2011) or 99mTc-tilmanocept (June 1, 2013, to January 31, 2014) was performed. SLN appearance time and uptake, SLN pathology, proportion of positive SLNs removed, and pain scores were compared for each radiopharmaceutical using the χ2 test, Fisher exact test, and unequal variance t test, as appropriate. Results: In total, 76 patients, with 86 evaluated axillae, underwent lymphoscintigraphy: 29 with 99mTc-SC and 47 with 99mTc-tilmanocept. The mean SLN appearance time was 11.0 min for 99mTc-SC and 19.3 min for 99mTc-tilmanocept (P = 0.003). There was no difference in the mean transit uptake percentage: 2.2% for 99mTc-SC and 1.9% for 99mTc-tilmanocept (P = 0.55). 99mTc-tilmanocept identified a greater proportion of intraoperative blue nodes than did 99mTc-SC (P = 0.03). There was no significant difference between 99mTc-SC and 99mTc-tilmanocept in the number of SLNs removed, number of patients with positive SLNs, or pain score. Conclusion: 99mTc-SC use in lymphoscintigraphy is an acceptable alternative to 99mTc-tilmanocept for SLN detection in breast cancer, on the basis of the similarity in intraoperative SLN identification and pain scores.

Benign granulomatous processes such as fungal infection may mimic metastatic lung cancer on FDG PET/CT. We found that these processes often have draining lymph node(s) with equal or greater FDG activity than associated lung nodule(s), a "flip-flop" of what is commonly seen in lung cancer. The aim of this study was to examine the utility of this "flip-flop fungus" (FFF) sign for diagnosing benign pulmonary disease. FDG PET/CT scans performed between 9/09-3/13 for the indications of pulmonary nodule or mass were reviewed. Scans with at least one hilar or mediastinal FDG avid draining node were included. Patients with a history of cancer, lack of pathologic confirmation, or without at least two years of imaging follow-up were excluded. A total of 209 FDG PET/CT exams were included and reviewed in a blinded fashion. A positive FFF sign had a sensitivity of 60.0% (95% CI: 47.6-71.5%) and specificity of 84.9% (95% CI: 77.8-90.4%) (P<0.0001) for benign disease. With additional strict imaging criteria applied, the FFF sign had a specificity of 98.6% (95% CI: 94.9-99.8%) (P<0.0001) and a positive predictive value of 90.0% (95% CI: 68.3-98.5%). A positive FFF sign was predominately due to granulomatous disease (91%), mostly histoplasmosis (73%). A positive FFF sign combined with positive fungal serology (n=16) had a specificity of 100% for benign disease. The FFF sign predicts benign disease in patients with a lung nodule(s) and an FDG avid draining lymph node(s) that would otherwise be considered worrisome for cancer.

This chapter discusses indications for, and techniques of, contrast lymphangiography. It discusses the role of computed tomography and magnetic resonance lymphangiography (MRL) in practice. Lymphatic evaluation with MRL is garnering increased interest due to its ability to visualize both lymphatic channels and lymph nodes. The role of MRL in patients with chylothorax or chylous ascites is in flux and is a source of ongoing investigation. At many institutions, MRL is performed to evaluate the cisterna chyli prior to a planned thoracic duct embolization procedure. The MRL technique depends on the indication and body part being imaged. Lymphangiectasia and lymphedema are evolving indications, and MRL is not currently a mainstay of evaluation for these patients. Lymphoscintigraphy has become quite useful in the evaluation of patients who are being considered for direct lymphatic reconstruction. Careful selection of patients and routine precautions are to the success of this invasive procedure.

Choline positron emission tomography (PET)/computed tomography (CT), with both carbon 11 (C-11) choline and fluorine 18 (F-18) choline, is an increasingly used tool in the evaluation of patients with biochemically recurrent prostate cancer. It has allowed detection and localization of locally recurrent and metastatic lesions that were difficult or impossible to identify using more conventional modalities. Many of the patients followed for their prostate cancer are elderly and have a higher rate of nonprostate cancer lesions or malignancies. As our experience with choline PET/CT has grown, it has become apparent that many of these nonprostate cancer processes, both benign and malignant, can be detected. Invasive thymoma, renal cell carcinoma, papillary thyroid carcinoma, and parathyroid adenoma are a few of the processes that have been incidentally detected with C-11-choline PET/CT at our institution and have significantly altered subsequent clinical management of the patient. Although most of the secondary lesions are detected due to their increased C-11-choline avidity, several have been detected due to their decreased or lack of avidity in the background of a highly avid organ. For instance, large liver masses that are relatively non-choline-avid create large activity defects in the otherwise highly active liver. Familiarity with normal C-11-choline physiologic activity, the most common prostate metastatic patterns, and imaging characteristics of secondary lesions is essential for the detection and correct diagnosis of such lesions so that proper follow-up and management can be recommended. (C) RSNA, 2016.

Choline positron emission tomography (PET)/computed tomography (CT), with both carbon 11 ((11)C) choline and fluorine 18 ((18)F) choline, is an increasingly used tool in the evaluation of patients with biochemically recurrent prostate cancer. It has allowed detection and localization of locally recurrent and metastatic lesions that were difficult or impossible to identify using more conventional modalities. Many of the patients followed for their prostate cancer are elderly and have a higher rate of nonprostate cancer lesions or malignancies. As our experience with choline PET/CT has grown, it has become apparent that many of these nonprostate cancer processes, both benign and malignant, can be detected. Invasive thymoma, renal cell carcinoma, papillary thyroid carcinoma, and parathyroid adenoma are a few of the processes that have been incidentally detected with (11)C-choline PET/CT at our institution and have significantly altered subsequent clinical management of the patient. Although most of the secondary lesions are detected due to their increased (11)C-choline avidity, several have been detected due to their decreased or lack of avidity in the background of a highly avid organ. For instance, large liver masses that are relatively non-choline-avid create large activity defects in the otherwise highly active liver. Familiarity with normal (11)C-choline physiologic activity, the most common prostate metastatic patterns, and imaging characteristics of secondary lesions is essential for the detection and correct diagnosis of such lesions so that proper follow-up and management can be recommended.

This practice parameter is for both FDG and amyloid brain PET or PET/computed tomography (CT) for patients with cognitive decline, and has been developed collaboratively by the American College of Radiology (ACR) and the American Society for Neuroradiology (ASNR). It is estimated that the number of people with dementia, 36.5 million worldwide in 2010, will increase to 65.7 million in 2030 and to 115 million in 2050. Four primary neurodegenerative etiologies of dementia have been defined: Alzheimer disease (AD), vascular dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Alzheimer disease is the most common form of dementia, accounting for approximately 60%-80% of all cases. Indications for FDG and amyloid brain PET and qualifications for personnel are discussed in this practice parameter.

OBJECTIVE:Multimodality imaging plays an important role in the structural and functional characterization of neurodegenerative conditions. This article illustrates the basic concepts of anatomic, metabolic, and amyloid imaging and describes the application of a multimodality approach in the evaluation of patients with the more common neurodegenerative dementia processes. Proper utilization of clinically available imaging techniques allows greater insight into these common disease processes.CONCLUSION:Recognizing the strength of combined anatomic, metabolic, and amyloid imaging can allow a more complete and confident assessment of patients with common degenerative dementias. This added knowledge can improve clinical care, allow initiation of appropriate therapies and counseling, and improve prognostication.

Whole-body fluorine 18 fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) is performed primarily for oncologic indications; however, FDG uptake is not specific for malignancy. Herein we focus on causes of increased FDG uptake in and around joints, as lesions in these locations are commonly benign. A combination of primary intra-articular processes and osseous processes that may occur near the joint space will be discussed. Causes of intra-articular and periarticular increased FDG activity can be broadly divided into infectious, inflammatory, degenerative, and benign neoplastic categories. A familiarity with the full range of these processes is important to avoid misinterpretation, in turn decreasing unnecessary follow-up studies, procedures, and treatments. Differentiation from malignancy is often possible on the basis of a different level of FDG activity, divergent response to therapy, or differing changes over time, in comparison with a patient's known primary cancer. Recognizing an intra-articular lesion location can also be critical, as intra-articular metastases are rare. In some cases, benign FDG-avid articular and periarticular entities have a specific appearance at FDG PET/CT and a correct diagnosis may be made without any additional workup. In most other cases, comparison with prior studies and/or additional imaging can afford an accurate diagnosis. This review is meant to introduce the reader to a spectrum of benign FDG-avid articular and periarticular processes that may be encountered at oncologic FDG PET/CT to increase confidence and diagnostic accuracy. (©)RSNA, 2016.

OBJECTIVE:The purpose of this article is to describe the role of multimodality imaging in the evaluation of atypical neurodegenerative conditions. An imaging approach to the more common dementia disease processes was described in part 1. This article, part 2, briefly discusses current Centers for Medicare & Medicaid Services coverage for imaging patients with dementia and illustrates the basic concepts of combining anatomic, metabolic, and amyloid imaging in the evaluation of patients with atypical neurodegenerative dementia. Although these disease processes are rare, the growing repertoire of clinically available imaging techniques necessitates an understanding of their imaging patterns.CONCLUSION:Despite the rarity of these conditions, imaging of patients with neurodegenerative disorders is on the rise, and familiarity with the imaging appearances of these atypical causes is increasingly important.

Multiple myeloma is a common hematologic malignancy among the elderly population. Although there have been many advances in treatment over the past few decades, the overall prognosis for the disease remains poor. Conventional radiography has long been the standard of reference for the imaging of multiple myeloma. However, 10%-20% of patients with multiple myeloma do not have evidence of disease at conventional radiography. There is a growing body of evidence supporting use of magnetic resonance (MR) imaging and 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in diagnosis and management of multiple myeloma. MR imaging is useful in detection of bone marrow infiltration, a finding often missed at conventional radiography. FDG PET/CT is especially sensitive for the detection of extramedullary disease and can help detect the metabolically active lesions that often precede evidence of osseous destruction at conventional radiography. MR imaging and FDG PET/CT are useful tools that can provide essential information for diagnosis and management of patients with multiple myeloma. Both modalities allow accurate localization of disease after chemotherapy or autologous stem cell transplantation and can provide important prognostic information that can influence further clinical decision making regarding therapy, particularly when tumor serum markers may be a less reliable indicator of disease burden after repeated treatments.

BackgroundThe utility of diagnostic imaging in paraneoplastic autoimmune multiorgan syndrome (PAMS) is unknown.MethodsWe examined the role of diagnostic imaging in patients with PAMS evaluated at our tertiary referral center (at Mayo Clinic, Rochester, MN, USA) and in the English literature between January 1, 1996, and August 31, 2012.ResultsWe included 17 patients from our institution and 208 patients from the literature review. Of these 225 patients, 113 (50.2%) were not known to have a malignancy diagnosis at the time of PAMS diagnosis. Of the 123 patients from our institution and from the literature reported to undergo imaging studies, conventional computed tomography (CT) was the predominant imaging modality (n=110; 89.4%); 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT was also used, albeit infrequently (n=12; 9.8%). When CT was included in imaging to identify or confirm the presence of a malignancy, imaging was successful in all patients who ultimately were diagnosed with an associated malignancy. At our institution, a relatively high percentage (n=7; 41%) of patients had 18F-FDG PET/CT, which not only identified all tumors found on CT but also facilitated staging of lymphoma and guided biopsy procedures.ConclusionDiagnostic imaging is frequently utilized in PAMS with unknown malignancy. Both conventional CT and 18F-FDG PET/CT are likely to detect the typical underlying neoplasms. Relative to conventional CT, 18F-FDG PET/CT may provide additional useful information regarding prognosis for the likely underlying malignancies, although there is a paucity of reports describing the use of this modality for this purpose.

This article presents a review of multiple myeloma, precursor states, and related plasma cell disorders. The clinical roles of fluorodeoxyglucose PET/computed tomography (CT) and the potential to improve the management of patients with multiple myeloma are discussed. The clinical and research data supporting the utility of PET/CT use in evaluating myeloma and other plasma cell dyscrasias continues to grow.

The advances in PET scanning for thoracic diseases that are deemed most likely to have clinical impact in the near-term future are highlighted in this article. We predict that the current practice of medicine will continue to embrace the power of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET scanning will continue to evolve and will expand into imaging of inflammatory disorders. New clinically available PET scan radiotracers, such as PET scan versions of octreotide and amyloid imaging agents, will expand PET imaging into different disease processes. Major improvements in thoracic PET/CT imaging technology will become available, including fully digital silicone photomultipliers and Bayesian penalized likelihood image reconstruction. These will result in significant improvements in image quality, improving the evaluation of smaller lung nodules and metastases and allowing better prediction of prognosis. The birth of clinical PET/MRI scan will add new imaging opportunities, such as better PET imaging of pleural diseases currently obscured by complex patient motion.

This article presents a review of multiple myeloma, precursor states, and related plasma cell disorders. The clinical roles of fluorodeoxyglucose PET/computed tomography (CT) and the potential to improve the management of patients with multiple myeloma are discussed. The clinical and research data supporting the utility of PET/CT use in evaluating myeloma and other plasma cell dyscrasias continues to grow.

BACKGROUND: Mammalian target of rapamycin (mTOR) signaling plays a critical role in tumor cell function and mTOR inhibitors have demonstrated promising activity in glioblastoma multiforme (GBM). Nevertheless, robust genetic predictors for sensitivity to mTOR inhibition remain elusive. As part of the biomarker discovery process, the North Central Cancer Treatment Group (NCCTG) incorporated functional imaging with 18FLT-PET/CT and focused exon sequencing into N057K, a Phase II clinical trial evaluating the mTORC1 inhibitor everolimus in combination with radiation(RT) and temozolomide(TMZ) in newly diagnosed GBM patients. METHODS: N057K began weekly everolimus one week prior to standard RT/TMZ. Patients who had >1cm3 of residual tumor were imaged with 18FLT-PET/CT before and after the initial two doses of everolimus, before initiating RT/TMZ. Imaged patients with a ΔSUVmax of >25% were classified as metabolic responders adapted from EORTC criteria for FDG-PET. Imaged patients with sufficient tumor samples also underwent immunohistochemical and focused exon sequencing analysis using the Seqwright 201 gene panel. Tertiary analysis focused on genes implicated in the PI3K/Akt/mTOR pathway (PTEN, PIK3CA, AKT, mTOR, Raptor/Rictor, S6, TSC1/2, NF1, CCND1, FGFR1/2). RESULTS: Nine patients had 18FLT-PET/CT imaging of which 4/9 had a metabolic response to everolimus alone. Six patients had sufficient tumor samples for further analysis, of which 3/6 had response. On IHC, 18FLT-PET responders had higher levels of PTEN expression and lower levels of pAKT and Ki-67 expression in comparison to non-responders. Focused exon sequencing found 1,458 coding alterations in 454 genes when compared to the reference genome. Only one 18FLT-PET responder had any genetic alterations within a PI3K/Akt/mTOR-implicated pathway, while all 18FLT-PET non-responders had multiple alterations within PI3K/Akt/mTOR-implicated pathways. CONCLUSIONS: 18FLT-PET successfully identified cohorts of patients who had robust, early metabolic responses to mTOR inhibition alone. These responders had robust PTEN expression on IHC and were less likely to have alterations within PI3K/Akt/mTOR-implicated pathways.

We sought to analyze the findings on DaTscan among patients with idiopathic REM sleep behavior disorder (iRBD), amnestic mild cognitive impairment (aMCI), nonamnestic MCI (naMCI), Alzheimer's dementia (ADem) and dementia with Lewy bodies (DLB). Reduced striatonigral uptake on DaTscan reflects dopamine deficiency, and this finding is typical of DLB. One would predict that those clinical syndromes associated with underlying Lewy body disease (LBD) pathology (eg, iRBD, naMCI and DLB) are more likely to have reduced striatonigral uptake compared to those with a non-LBD substrate (eg, aMCI and ADem). DaTscan imaging was performed 3-6 hours after injection of 3-5 mCI of 123 I Ioflupane (DaTscan). Regions of interest (ROIs) were placed over the right and left putamen and occipital cortices in each subject. The mean of the right and left putamen to occipital ratios (mPOR), presence/absence of RBD, and total score on the motor subtest of the Unified Parkinson's Disease Rating Scale (UPDRS) for each patient were analyzed. 56 subjects (mean age 68 ± 9 years, 45 male) underwent DaTscan, of whom 5 have iRBD and 32 have RBD coexisting with cognitive impairment ± parkinsonism. The mPOR±SD for each syndrome is aMCI (n=8): 2.46±0.42, ADem (n=11): 2.47±0.66, iRBD (n=5): 2.46±0.65, naMCI (n=13): 2.26±0.61, and DLB (n=19): 1.64±0.65 (aMCI, ADem and iRBD > DLB, p<0.05). Using a cut-off mPOR value of 2.2, the frequency considered low for each diagnosis is aMCI: n=2 (25%, 1 with RBD), ADem: n=2 (18%, both with RBD), iRBD: n=1 (20%), naMCI: n=7 (54%, all 7 with RBD), and DLB: n=15 (79%, all 15 with RBD). RBD is associated with a lower mPOR (1.92 vs 2.60, p<0.001) and higher likelihood of mPOR value <2.2 (68% vs 6 %, p<0.001). UPDRS is negatively correlated with mPOR (r=-0.6147, p<0.001). These findings suggest that 1) striatonigral uptake in aMCI and ADem is more likely to be normal, whereas naMCI and DLB is more likely to be low, and 2) the presence of RBD and/or higher UPDRS score is associated with reduced mPOR. These findings support the potential utility of DaTscan in demonstrating dopamine deficiency and presumed LBD regardless of the clinical syndrome. Study supported by: UO1 AG006786, P50 AG016574, RO1 AG015866, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, and the Mangurian Foundation.

Patients with DLB have reduced striatonigral uptake on DaTscan consistent with dopamine deficiency, a pattern not observed in AD. While motor associations of DaTscan results are known, non-motor, neuropsychiatric features require further investigation. DLB patients may experience apathy, depression, hallucinations, anxiety and delusions. We sought to determine whether different neuropsychiatric features are associated with DaTscan striatonigral uptake in DLB. DaTscan imaging was performed 3-6 hours after injection of 3-5 mCI of 123 I Ioflupane (DaTscan). Circular ROIs were placed over the right and left putamen and caudate of each subject. Identical ROIs were placed over ipsilateral occipital cortical tissue. The means of the right and left putamen to occipital ratios (mPOR) and caudate to occipital ratios (mCOR) of uptake were analyzed and compared with presence/absence of apathy, depression, hallucinations, anxiety and depression as measured by the Neuropsychiatric Inventory for DLB patients. Since non-amnestic mild cognitive impairment (naMCI) patients and amnestic MCI patients with REM sleep behavior disorder (aMCI/RBD) are more likely to progress to DLB, these patients were analyzed with DLB. 19 DLB patients (mean age 69.5 years, 17 male), 13 naMCI patients (mean age 66.7 years, 12 male, 11 with RBD), and 2 aMCI/RBD patients (mean age 74, 1 male) underwent DaTscan. The mPOR ± SD was 1.89±0.7 and mCOR was 2.16±0.7. Apathy was present in 13/19 DLB, 7/13 naMCI and 1/2 with aMCI/RBD. DLB patients with apathy had decreased uptake in the caudate (p=0.008) and putamen (p=0.04). The presence of hallucinations, depression, anxiety, and delusions was not associated with uptake in the putamen or caudate. Apathy is associated with reduced striatonigral uptake in DLB and MCI at risk for DLB. This finding is consistent with lesional studies of the caudate where the most common behavioral abnormality is apathy and the notion that apathy in Parkinson's related disorders is partially dopamine dependent. More work is needed to determine if apathy in DLB is associated with disruption of the frontostriatnonigral networks and/or other core clinical DLB features or neurochemical systems.