Ismini C. Mainta

PET/MR in Breast Cancer

Breast cancer is an international public health concern in which an optimal treatment plan requires a precise staging. Both MRI and PET imaging techniques have made significant progress in the last decades with constant improvements that made both modalities clinically relevant in several stages of breast cancer management and follow-up. On one hand, specific breast MRI permits high diagnostic accuracy for local tumor staging, and whole-body MRI can also be of great use in distant staging, eventually accompanied by organ-specific MRI sequences. Moreover, many different MRI sequences can be performed, including functional MRI, letting us foresee important improvements in breast cancer characterization in the future. On the contrary, (18)F-FDG-PET has a high diagnostic performance for the detection of distant metastases, and several other tracers currently under development may profoundly affect breast cancer management in the future with better determination of different types of breast cancers allowing personalized treatments. As a consequence PET/MR is a promising emerging technology, and it is foreseeable that in cases where both PET and MRI data are needed, a hybrid acquisition is justified when available. However, at this stage of deployment of such hybrid scanners in a clinical setting, more data are needed to demonstrate their added value beyond just patient comfort of having to undergo a single examination instead of two, and the higher confidence of diagnostic interpretation of these co-registered images. Optimized imaging protocols are still being developed and are prone to provide more efficient hybrid protocols with a potential improvement in diagnostic accuracy. More convincing studies with larger number of patients as well as cost-effectiveness studies are needed. This article provides insights into the current state-of-the-art of PET/MR in patients with breast cancer and gives an outlook on future developments of both imaging techniques and potential applications in the future.

FDG PET/MR Imaging in Major Neurocognitive Disorders

PET/MRI tomographs represent the latest development in hybrid molecular imaging, opening new perspectives for clinical and research applications and attracting a large interest among the medical community. This new hybrid modality is expected to play a pivotal role in a number of clinical applications and among these the assessment of neurodegenerative disorders. PET and MRI, acquired separately, are already the imaging biomarkers of choice for a comprehensive assessment of the changes occurring in dementias (major cognitive disorders) as well as in their prodromal phase. In this paper we review the current evidence on the use of integrated PET/MRI scanners to investigate patients with neurodegenerative conditions, and in particular major neurocognitive disorders. The number of studies performed is still limited and shows that the use of PET/MRI gives results overall comparable to PET/CT and MRI acquired independently. We also address the challenges for quantitative aspects in PET/MRI, namely attenuation, partial volume and motion correction and the use of semi-quantitative approaches for FDG PET image analysis in this framework. The recent development of PET tracers for the in vivo differential diagnosis of dementias, able to visualize amyloid and tau deposits, suggests that in the future PET/MRI might represent the investigation of choice for a single session evaluation of morphological, functional and molecular markers.

High protracted 99mTc-HDP uptake in synthetic bone implants — A potentially misleading incidental finding on bone scintigraphy

We report the case of a 56-year-old male with bilateral total knee prostheses suffering from bilateral knee pain mainly on the right side and referred for bone scintigraphy. The medical history of the patient revealed an opening wedge high tibial osteotomy performed nine years earlier, with insertion of two blocks of ceramic made of hydroxyapatite and tricalcium phosphate in a wedge configuration as synthetic bone substitutes. The porous structure of these implants is analogous to the architecture of cancellous bone and permits fibrovascular and bone ingrowth, promoting the healing process. Planar scintigraphy and SPECT/CT showed an intense uptake within those implants in the early phase as well as in the late phase of the bone scan. It also showed bilateral patellofemoral arthritis. A (99m)Tc-labeled antigranulocyte antibody scintigraphy was negative for infection or inflammation. Bilateral patellar resurfacing led to complete symptom regression, confirmed at 10 months follow-up. To the best of our knowledge, this scintigraphic pattern with such a high tracer uptake reflecting bone substitute osteointegration has not yet been published. This should be considered in patients with such bone replacement materials that are increasingly used, in order to avoid false diagnosis of inflammation or infection.

Dopaminergic denervation is not necessary to induce gait disorders in atypical parkinsonian syndrome

BACKGROUND Gait impairment is common in parkinsonian syndromes but not specific to striatonigral dysfunction. The relationship between the dopaminergic system and gait parameters is poorly understood. This cross-sectional study aimed to determine if gait measures are related to the striatal dopamine transporters distribution using [(123)I]FP-CIT SPECT in patients with parkinsonian syndromes. MATERIALS AND METHODS Twenty-four patients with gait impairment and parkinsonian syndromes without Parkinsons disease (mean age: 73.6±8.2years) were included in this study. Gait analysis during single- and dual-task condition (walking and backwards counting) and [(123)I]FP-CIT SPECT were performed within 3months of each other. Patients were visually categorized as having normal (n=14) or abnormal (n=10) [(123)I]FP-CIT SPECT. In addition, a volume-of-interest-based analysis of uptake ratios (caudate and putamen) relative to the occipital cortex and a voxelwise analysis using SPM8 were also performed. RESULTS Patients with parkinsonian syndromes and abnormal [(123)I]FP-CIT SPECT did not significantly differ in terms of spatiotemporal gait parameters from those with normal [(123)I]FP-CIT SPECT. Moreover, after correction for multiple comparisons, we did not observe any association between regional uptake ratio and spatiotemporal gait parameters for single and dual tasking. Finally, none of these parameters showed a significant association with voxelwise [(123)I]FP-CIT uptake. CONCLUSIONS Dopaminergic denervation, as measured by [(123)I]FP-CIT SPECT, is not necessary to induce alterations of spatiotemporal gait parameters during single and dual task in patients presenting with atypical parkinsonian syndromes.

Severe early basal ganglia hypometabolism in neurodegeneration with brain iron accumulation.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare genetic neurological disorders characterized by iron deposits in the basal ganglia. Apart from the iron accumulation identified on MRI, the role of imaging modalities is limited [1]. Here we present the metabolic findings in a 45-year-old man with NBIA. After a 14year history of psychiatric symptoms, the patient was referred to our institution for cognitive decline and parkinsonian symptoms, which had developed progressively during the previous 4 years. Brain MRI showed global atrophy and iron accumulation in the caudate and dentate nuclei, putamen, globus pallidus and substantia nigra, bilaterally, as signal hypointensities on the gradient echo T2 sequence (a). Further investigation by F-FDG PET revealed severe metabolic reduction exclusively in the basal ganglia, as shown on the PET/ MRI image (b), the PET image (c) and the BRASS software deviation image (d), that was retrospectively found to be already decreased on a previous PET scan performed 12 years earlier when the MRI scan was still normal. Cortical, thalamic and cerebellar metabolism was within the normal range, contrary to previous reports in NBIA [2, 3]. This metabolic pattern is typically associated with Huntington’s disease (HD), in which the caudate and putamen are already affected in the preclinical phase of the disease, with gradual cortical involvement [4]. Early iron accumulation in the basal ganglia has been found in HD as well, but the typical finding is marked atrophy of the caudate nuclei with ex-vacuo dilatation of * Ismini C. Mainta isminicharis.mainta@hcuge.ch

PET/MRI in Breast Cancer

Breast cancer is the most common cancer in women worldwide, and represented more than 25% of the newly diagnosed cancer cases in women in 2016. PET/CT is recommended in the clinical workup of advanced breast cancers and in cases of breast cancer recurrence and may also be proposed in treatment monitoring. PET/MRI is a new imaging technique which is now being used clinically in different countries, and which may replace PET/CT in some selected breast cancer patients, when available. A detailed description of advantages and indications of, respectively, PET and MRI techniques taken separately in breast cancer patients is beyond the scope of the present work and has already been reviewed elsewhere by our group. We focused on the technical advantages and disadvantages of combined PET/MRI acquisitions in breast cancer patients from diagnosis to follow-up. In this chapter, we cover the specifics of PET/MRI in terms of quantification and provide a summary of the different protocols performed in breast cancer PET/MRI imaging. We will also discuss the clinical advances for patient management, the potential improvements that may occur in the future, as well as the future role that may be given to this technique.

Education-Adjusted Normality Thresholds for FDG-PET in the Diagnosis of Alzheimer Disease

Background: A corollary of the reserve hypothesis is that what is regarded as pathological cortical metabolism in patients might vary according to education. Objective: The aim of this study is to assess the incremental diagnostic value of education-adjusted over unadjusted thresholds on the diagnostic accuracy of FDG-PET as a biomarker for Alzheimer disease (AD). Methods: We compared cortical metabolism in 90 healthy controls and 181 AD patients from the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The AUC of the ROC curve did not differ significantly between the whole group and the higher-education patients or the lower-education subjects. Results: The threshold of wMetaROI values providing 80% sensitivity was lower in higher-education patients and higher in the lower-education patients, compared to the standard threshold derived over the whole AD collective, without, however, significant changes in sensitivity and specificity. Conclusion: These data show that education, as a proxy of reserve, is not a major confounder in the diagnostic accuracy of FDG-PET in AD and the adoption of education-adjusted thresholds is not required in daily practice.

Hybrid PET-MRI in Alzheimer’s Disease Research

Multiple factors, namely amyloid, tau, inflammation, metabolic, and perfusion changes, contribute to the cascade of neurodegeneration and functional decline occurring in Alzheimers disease (AD). These molecular and cellular processes and related functional and morphological changes can be visualized in vivo by two imaging modalities, namely positron emission tomography (PET) and magnetic resonance imaging (MRI). These imaging biomarkers are now part of the diagnostic algorithm and of particular interest for patient stratification and targeted drug development.In this field the availability of hybrid PET/MR systems not only offers a comprehensive evaluation in a single imaging session, but also opens new possibilities for the integration of the two imaging information. Here, we cover the clinical protocols and practical details of FDG, amyloid, and tau PET/MR imaging as applied in our institutions.

Dopaminergic imaging separates normal pressure hydrocephalus from its mimics

ObjectiveIdiopathic normal pressure hydrocephalus (iNPH) and iNPH mimics (i.e., Parkinson’s disease, progressive supranuclear palsy or dementia with Lewy bodies) share similar clinical features, and discrimination between both conditions relies on invasive time-consuming investigations. This study aims to compare [123I]FP-CIT SPECT imaging—visual rating and semiquantitative values—between iNPH and iNPH mimics.MethodsAmong 56 patients with a suspicion of iNPH (76.5 ± 6.1 years; 23.2% women), 26 fulfilled the iNPH diagnostic criteria and the remaining 30 were classified as iNPH mimics. Patients were visually categorized as having normal or abnormal [123I]FP-CIT SPECT; and for the quantification of the [123I]FP-CIT SPECT imaging, we calculated striatal binding ratios (SBR) using BRASS™ automated brain analysis while applying locally established reference limits (adjusted for age). Logistic regressions were used to assess the association between [123I]FP-CIT SPECT and diagnostic groups.ResultsA normal SBR [123I]FP-CIT SPECT was present in 69.2% of iNPH and 37.9% of mimics (p value = .020), while visual rating did not differ between the two groups. Normal SBR [123I]FP-CIT SPECT values were associated with the diagnosis of iNPH, even after adjusting for white matter changes and comorbidities (adjusted odds ratio: 4.17; 95% CI 1.26–13.80).ConclusionSemi-quantitative [123I]FP-CIT SPECT evaluation, but not visual assessment, discriminates iNPH patients from their mimics. [123I]FP-CIT SPECT represents an interesting neuroimaging biomarker to improve the selection of patients with iNPH for invasive shunt surgery.

What is the diagnostic performance of 18-FDG-PET/MR compared to PET/CT for the N- and M- staging of breast cancer?

PurposeTo compare the diagnostic performance of 18-FDG-PET/MR and PET/CT for the N- and M- staging of breast cancer.Methods and materialsTwo independent readers blinded to clinical/follow-up data reviewed PET/MR and PET/CT examinations performed for initial or recurrent breast cancer staging in 80 consecutive patients (mean age = 48 ± 12.9 years). The diagnostic confidence for lesions in the contralateral breast, axillary/internal mammary nodes, bones and other distant sites were recorded. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. The standard of reference included pathology and/or follow-up > 12 months.ResultsNine of 80 patients had bone metastases; 13/80 had other distant metastases, 44/80 had axillary, 9/80 had internal mammary and 3/80 had contralateral breast tumours. Inter-reader agreement for lesions was excellent (weighted kappa = 0.833 for PET/CT and 0.823 for PET/MR) with similar reader confidence for the two tests (ICC = 0.875). In the patient-per-patient analysis, sensitivity and specificity of PET/MRI and PET/CT were similar (p > 0.05). In the lesion-per-lesion analysis, the sensitivity of PET/MR and PET/CT for bone metastases, other metastases, axillary and internal mammary nodes, contralateral tumours and all lesions together was 0.924 and 0.6923 (p = 0.0034), 0.923 and 0.923 (p = 1), 0.854 and 0.812 (p = 0.157), 0.9 and 0.9 (p = 1), 1 and 0.25 (p = 0.083), and 0.89 and 0.77 (p = 0.0013) respectively. The corresponding specificity was 0.953 and 1 (p = 0.0081), 1 and 1 (p = 1), 0.893 and 0.92 (p = 0.257), 1 and 1 (p = 1), 0.987 and 0.99 (p = 1) and 0.96 and 0.98 (p = 0.0075) respectively.ConclusionsReader confidence, inter-reader agreement and diagnostic performance per patient were similar with PET/MR and PET/CT. However, for all lesions together, PET/MR had a superior sensitivity and lower specificity in the lesion-per-lesion analysis.Key Points• N and M breast cancer staging performance of PET/MR and PET/CT is similar per patient.• In a lesion-per-lesion analysis PET/MR is more sensitive than PET/CT especially for bone metastasis.• Readers’ diagnostic confidence is similar for both tests.