Multimodality Imaging of Neurodegenerative Processes: Part 2, Atypical Dementias.

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.

Multimodality Imaging of Neurodegenerative Processes: Part 1, The Basics and Common Dementias.

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.

Spectrum of Benign Articular and Periarticular Findings at FDG PET/CT.

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.

¹¹C-Choline PET/CT in Recurrent Prostate Cancer and Nonprostatic Neoplastic Processes.

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.

MR imaging and PET/CT in diagnosis and management of multiple myeloma.

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.

Structural and functional imaging in parkinsonian syndromes.

Movement disorders with parkinsonian features are common, and in recent years imaging has assumed a greater role in diagnosis and management. Thus, it is important that radiologists become familiar with the most common imaging patterns of parkinsonism, especially given the significant clinical overlap and diagnostic difficulty associated with these disorders. The authors review the most common magnetic resonance (MR) and molecular imaging patterns of idiopathic Parkinson disease and atypical parkinsonian syndromes. They also discuss the interpretation of clinically available molecular imaging studies, including assessment of cerebral metabolism with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET), cortical amyloid deposition with carbon 11 ((11)C) Pittsburgh compound B and fluorine 18 ((18)F) florbetapir PET, and dopaminergic activity with iodine 123 ((123)I) ioflupane single photon emission computed tomography (SPECT). Although no single imaging test is diagnostic, a combination of tests may help narrow the differential diagnosis. Findings at (123)I ioflupane SPECT can confirm the loss of dopaminergic neurons in patients with parkinsonism and help distinguish these syndromes from treatable conditions, including essential tremor and drug-induced parkinsonism. FDG PET uptake can demonstrate patterns of neuronal dysfunction that are specific to a particular parkinsonian syndrome. Although MR imaging findings are typically nonspecific in parkinsonian syndromes, classic patterns of T2 signal change can be seen in multiple system atrophy and progressive supranuclear palsy. Finally, positive amyloid-binding PET findings can support the diagnosis of dementia with Lewy bodies. Combined with a thorough clinical evaluation, multimodality imaging information can afford accurate diagnosis, allow selection of appropriate therapy, and provide important prognostic information.

Malignant involvement of the peripheral nervous system in patients with cancer: multimodality imaging and pathologic correlation.

The clinical and imaging evaluation of peripheral neuropathies in patients with cancer is challenging. It is critically important to differentiate malignant invasion of the peripheral nervous system from nonmalignant causes, such as radiation-induced neuritis, neuropathy associated with chemotherapy, and inflammatory neuropathies. Contrast material-enhanced magnetic resonance (MR) imaging is the initial noninvasive test of choice; however, interpretation can be challenging when the anatomic features are distorted by prior surgery, radiation, or both. Fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an imaging adjunct to MR imaging that is particularly helpful for evaluating peripheral nerves because the metabolic activity depicted with (18)F-FDG PET/CT helps differentiate malignant from benign disease and assists in making certain management decisions. For example, sites of high (18)F-FDG activity in a peripheral nerve can be targeted to increase the diagnostic yield of a biopsy because malignant involvement of peripheral nerves can be patchy. Of note, (18)F-FDG PET/CT can show clinically unsuspected metastases elsewhere in the body. If cancer is found, (18)F-FDG PET/CT allows excellent assessment of treatment response. (18)F-FDG PET/CT is also useful in evaluating primary nerve sheath tumors in that such tumors with low metabolic activity on FDG PET/CT images are unlikely to be malignant, although the specificity is limited. It is essential to have a good understanding of the imaging characteristics of benign and malignant causes of peripheral neuropathy if (18)F-FDG PET/CT is to be used effectively for accurate diagnosis.

Thyroid cancer detection with dual-isotope parathyroid scintigraphy in primary hyperparathyroidism.

BACKGROUND: Thyroid cancer cells have been shown to take up (99m)Tc-sestamibi. The role for (99m)Tc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim was to determine whether dual-isotope parathyroid scintigraphy is useful in identifying thyroid cancer. METHODS: A prospective database of 3,187 patients who underwent neck exploration for PHPT was reviewed to identify patients who had concurrent thyroid resection. Patients with benign and malignant thyroid disease were comparatively analyzed. RESULTS: A total of 470 patients underwent both thyroidectomy and parathyroidectomy (reoperations in 21%). Benign disease (n = 391, 83%) was more common than malignancy [papillary thyroid cancer (n = 75) and medullary thyroid cancer (n = 5); 1 had both]. Dual-isotope scintigraphy obtained in 374 patients (80%) had a sensitivity of 67% and a positive predictive value of 66% for parathyroid adenoma localization in these patients with thyroid disease. False-positive scintigraphy occurred in 22% with benign and 45% with malignant thyroid disease (P = 0.002). On Tc-MIBI imaging, 54 (86%) of 63 patients with malignancy had hot nodules, compared to 248 (81%) of 308 patients with benign disease (P = 0.49). On I-123 imaging, 34 (54%) of 63 patients with malignancy had cold nodules, compared to 42 (14%) of 304 patients with benign disease (P < 0.001). A dual-isotype phenotype of both Tc-MIBI-Hot and I-123-Cold had sensitivity 52%, specificity 88%, positive predictive value 47%, and negative predictive value 90% for detecting a thyroid malignancy. CONCLUSIONS: A Tc-MIBI-Hot/I-123-Cold phenotype is very specific for detecting thyroid malignancy. Patients with this imaging phenotype should strongly be considered for preoperative ultrasound-guided biopsy. Patients found intraoperatively to have false-positive parathyroid scintigraphy should be evaluated for thyroid cancer.

PET/CT of cancer patients: part 1, pancreatic neoplasms.

OBJECTIVE: Pancreatic cancer continues to have a poor prognosis despite impressive improvements in the outcomes of many other types of cancer, often because most pancreatic neoplasms are found to be unresectable at diagnosis. The purpose of this review is to provide an overview of pancreatic cancer and the role of modern imaging in its diagnosis and management with an emphasis on (18)F-FDG PET/CT fusion imaging. CONCLUSION: Multimodality imaging is critical in the diagnosis and management of pancreatic cancer. PET/CT is increasingly viewed as a useful, accurate, and cost-effective modality in diagnosing and managing pancreatic cancer, but further studies are warranted. Early data suggest that contrast-enhanced PET/CT performed with modern PET/CT scanners yields high-resolution anatomic information for surgical and radiotherapeutic planning and functional information for whole-body staging in the care of patients with this disease.

The utility of 11C-choline PET/CT for imaging prostate cancer: a pictorial guide.

OBJECTIVE: The objective of this article is to provide an illustrative tutorial showing the utility of (11)C-choline PET/CT for imaging prostate cancer. CONCLUSION: Carbon-11-labeled choline PET/CT is a powerful adjunct to the currently available imaging modalities for evaluating prostate cancer. As with any diagnostic method, false-positives and false-negatives occur. However, these diagnostic errors can be reduced if readers are familiar with the normal and abnormal patterns of (11)C-choline distribution in the body.

Value of PET/CT in the management of liver metastases, part 1.

OBJECTIVE: Metastasis is the most common (95%) of liver lesions. Early diagnosis and staging are the keys to treatment planning and prognosis. There is a consistent benefit to the use of PET/CT for detecting hepatic, local, and distant metastases from a variety of primary malignancies, which can contribute to staging and ultimately helps to establish the best course of treatment and to determine prognosis. CONCLUSION: For colorectal cancer, FDG PET and FDG PET/CT are particularly effective for identification of additional hepatic and extrahepatic metastases, frequently upstaging the tumor stage and affecting management. In addition, PET/CT is very useful in local ablative and systemic therapy assessment and surveillance for liver metastases.

Value of PET/CT in the management of primary hepatobiliary tumors, part 2.

OBJECTIVE: Primary hepatobiliary malignancies consist of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder cancer. Benign hepatic lesions include hepatic cysts, hemagiomas, adenomas, and focal nodular hyperplasias. The utility of PET/CT in imaging primary hepatobiliary lesions varies according to the type and location of the lesion. CONCLUSION: There is a consistent benefit to the use of PET/CT for detection and staging, and it ultimately helps to establish the best course of treatment and to determine prognosis. In addition, PET/CT is very useful in local ablative and systemic therapy assessment and surveillance for hepatobiliary malignancies.

FDG PET/CT in patients with HIV.

OBJECTIVE: This article will discuss the (18)F-FDG normal variant uptake and the role of FDG PET/CT in malignancies in HIV-infected patients, CNS manifestations of HIV, assessing fever of unknown origin in HIV patients, assessing response to highly active antiretroviral therapy and assessing complications. CONCLUSION: FDG PET/CT is a valuable imaging study in the management of HIV-infected patients.

Induction versus no induction chemotherapy before neoadjuvant chemoradiotherapy and surgery in oesophageal adenocarcinoma: a multicentre randomised phase II trial (NCCTG N0849 [Alliance]).

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.

The value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography in extranodal natural killer/T-cell lymphoma.

PURPOSE: To our knowledge, there are no published data pertinent to the use of [(18F)]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with natural killer (NK)/T-cell lymphoma. The purpose of this study was to assess the value of FDG PET/CT in this aggressive type of non-Hodgkin lymphoma. PATIENTS AND METHODS: All patients with NK/T-cell lymphoma referred for FDG PET/CT at our institution from July 2001 to July 2006 were retrospectively studied. PET/CT examinations were blindly reviewed by 2 experienced readers. The results were compared with the status of the disease, which was determined after evaluation of biopsy, laboratory, clinical and conventional imaging examination, and follow-up results. PET/CT results were thereby classified as true-positive, true-negative, false-positive, or false-negative. The degree of FDG uptake in the positive lesions was semiquantified using maximum standard uptake value (SUV(max)). RESULTS: Twenty-one PET/CT examinations were performed in 10 patients with NK/T-cell lymphoma. For nasal disease, PET/CT was true-positive in 5 cases, true-negative in 15 cases, and positive but unconfirmed in 1 case. For extranasal disease, PET/CT was true-positive in 3 cases, true-negative in 16 cases, and false-negative in 2 cases. The mean SUV(max) in PET-positive lesions in nasal cavities or paranasal sinuses was 16 gm/mL (range, 5-25 gm/mL; median, 19.3 gm/mL). In extranasal disease, the mean SUV(max) was 10.9 gm/mL (range, 4.6-34.1 gm/mL; median, 5.6 gm/mL). CONCLUSION: Viable NK/T-cell lymphoma is intensely FDG hypermetabolic. PET/CT appears to be sensitive for the detection of disease in the nasopharynx and, to a lesser extent, in extranasal sites.

Pulmonary embolism outcome: a prospective evaluation of CT pulmonary angiographic clot burden score and ECG score.

OBJECTIVE: The purpose of this study was to establish whether a correlation exists between the CT pulmonary angiographic clot burden score, the ECG score at diagnosis, and the 12-month mortality rate among patients diagnosed with pulmonary embolism. SUBJECTS AND METHODS: A total of 523 consecutive patients who underwent CT pulmonary angiography for a suspected moderate to high pretest probability of pulmonary embolism were recruited from March 2003 to October 2004. There were 105 patients with positive CT pulmonary angiography examinations. Two consultant respiratory physicians and two consultant radiologists independently and prospectively calculated an ECG score and a quantified pulmonary artery clot burden, respectively. Twelve-month follow-up was completed in all patients. RESULTS: The mean ECG score was 2.36 (SD, 2.84) and the mean clot burden score percentage was 23.74% (16.8%). Poor correlation (r = 0.09) was seen between the average ECG score and the average clot burden score percentage (p = 0.39) at diagnosis. Thirteen patients had died at the 12-month follow-up. The mean ECG score for those patients who were alive was 2.4 (2.91) and for those who had died was 2.03 (2.34) at 12 months (p = 0.65). The mean clot burden score percentage for those patients who were alive was 24% (17%) and for those who had died was 22.1% (15.7%) at 12 months (p < 0.73). CONCLUSION: No statistically significant association was seen between ECG score and CT pulmonary angiographic clot burden at diagnosis and the 12-month all-cause mortality rate of patients diagnosed with pulmonary embolism.

Clinical significance of diffusely increased 18F-FDG uptake in the thyroid gland.

UNLABELLED: Our purpose was to determine the clinical significance of diffusely increased (18)F-FDG uptake in the thyroid gland as an incidental finding on PET/CT. METHODS: All patients who were found to have diffuse thyroid uptake on (18)F-FDG PET/CT in our institution between November 2004 and June 2006 were investigated and compared with an age- and sex-matched control group. The (18)F-FDG uptake in the thyroid was semiquantified using maximum standardized uptake value and correlated to the available serum thyroid-stimulating hormone (TSH) and thyroid peroxidase (TPO) antibody levels using regression analysis. RESULTS: Of the 4,732 patients, 138 (2.9%) had diffuse thyroid uptake. Clinical information was available for 133 of the 138 patients. Sixty-three (47.4%) had a prior diagnosis of hypothyroidism or autoimmune thyroiditis, of whom 56 were receiving thyroxine therapy. In the control group, consisting of 133 patients with no thyroid uptake, there were 13 (9.8%) with a prior diagnosis of hypothyroidism, 11 of whom were receiving thyroxine therapy. In the study group, 38 (28.6%) of 133 patients did not undergo any further investigation for thyroid disease, whereas 32 (24.1%) of 133 patients were examined for thyroid disease after PET. Nineteen were found with autoimmune thyroiditis or hypothyroidism, and replacement therapy was initiated in 12. No significant correlation was found between maximum standardized uptake value and TSH (P = 0.09) or TPO antibody (P = 0.68) levels. CONCLUSION: The incidental finding of increased (18)F-FDG uptake in the thyroid gland is associated with chronic lymphocytic (Hashimoto's) thyroiditis and does not seem to be affected by thyroid hormone therapy. SUV correlated neither with the degree of hypothyroidism nor with the titer of TPO antibodies.

18F-FDG PET/CT in primary central nervous system lymphoma in HIV-negative patients.

OBJECTIVE: To determine the value of F-FDG PET/CT in the different manifestations of primary central nervous system lymphoma (PCNSL) in HIV-negative patients. METHODS: All PCNSL and HIV-negative patients referred for PET/CT in our institution from July 2001 to June 2006 were retrospectively studied. PET/CT examinations were reviewed by two experienced readers and evaluated for each possible anatomical site of nervous system involvement: cerebral, spinal/nerve and ocular. PET/CT results were characterized as true positive or negative and false positive or negative according to the status of the disease, which was determined after the evaluation of biopsies, laboratory, clinical and imaging examinations, and follow-up. RESULTS: Forty-two PET/CT examinations were carried out in 25 PCNSL patients. For intracerebral disease, PET/CT was true positive in 13 cases, true negative in 27 and false negative in two. For disease involving spinal cord and/or nerves, PET/CT was true positive in four cases, true negative in 37 and false negative in one. For ocular disease, PET was true positive in only one case and false negative in four. The sensitivity of PET/CT in detecting active disease in the brain was 87% (13/15), in the spine/nerves 80% (4/5), and in the eyes only 20% (1/5). CONCLUSION: PET/CT seems to be sensitive for the detection of viable intracerebral as well as for spinal and peripheral nerve disease, but not for the detection of ocular involvement.

Contribution of F-18 FDG PET-CT in the detection of systemic spread of primary central nervous system lymphoma.

PURPOSE: Primary central nervous system lymphoma (PCNSL) accounts for approximately 3% of all primary brain tumors and 1% of all non-Hodgkin lymphomas. Detection of systemic spread of PCNSL, although rare (4%), is very important since therapy is usually modified. Contrast-enhanced computed tomography (CT) is commonly used for systemic staging of PCNSL. No previous case report is available in the published literature elaborating the potential contribution of F-18 FDG PET in systemic staging of PCNSL. The purpose of this case report was to document the potential usefulness of F-18 FDG-PET in the detection of occult systemic involvement in PCNSL. MATERIALS AND METHODS: A 50-year-old, immunocompetent, male patient completed successful treatment of PCNSL. As part of a routine pretransplant evaluation he had an F-18 FDG PET coregistered with CT (PET-CT). The PET-CT results were then compared with those of contrast-enhanced CT of the chest, abdomen, and pelvis. RESULTS: The PET-CT examination detected multiple sites of extranodal systemic disease that were not seen in the contrast-enhanced CT of the chest, abdomen, and pelvis (both studies were performed within 24 hours of each other). Percutaneous ultrasound guided biopsy confirmed the presence of systemic spread of PCNSL. The patient's subsequent therapy was modified to include rituximab with cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). A follow up PET-CT confirmed resolution of systemic spread. CONCLUSION: F-18 FDG PET coregistered to CT may be a useful examination in the detection and monitoring for systemic spread of the disease in PCNSL patients.