Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer’s disease?

Purpose

Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer’s disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD.

Methods

We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer’s Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia.

Results

In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy.

Conclusion

Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions.

     

Early identification of MCI converting to AD: a FDG PET study

Purpose

Mild cognitive impairment (MCI) is a transitional pathological stage between normal ageing (NA) and Alzheimer’s disease (AD). Although subjects with MCI show a decline at different rates, some individuals remain stable or even show an improvement in their cognitive level after some years. We assessed the accuracy of FDG PET in discriminating MCI patients who converted to AD from those who did not.

Methods

FDG PET was performed in 42 NA subjects, 27 MCI patients who had not converted to AD at 5 years (nc-MCI; mean follow-up time 7.5 ± 1.5 years), and 95 MCI patients who converted to AD within 5 years (MCI-AD; mean conversion time 1.8 ± 1.1 years). Relative FDG uptake values in 26 meta-volumes of interest were submitted to ANCOVA and support vector machine analyses to evaluate regional differences and discrimination accuracy.

Results

The MCI-AD group showed significantly lower FDG uptake values in the temporoparietal cortex than the other two groups. FDG uptake values in the nc-MCI group were similar to those in the NA group. Support vector machine analysis discriminated nc-MCI from MCI-AD patients with an accuracy of 89% (AUC 0.91), correctly detecting 93% of the nc-MCI patients.

Conclusion

In MCI patients not converting to AD within a minimum follow-up time of 5 years and MCI patients converting within 5 years, baseline FDG PET and volume-based analysis identified those who converted with an accuracy of 89%. However, further analysis is needed in patients with amnestic MCI who convert to a dementia other than AD.

     

Five-year follow-up of <Superscript>11</Superscript>C-PIB uptake in Alzheimer’s disease and MCI

Purpose

The aim of this study was to evaluate the longitudinal changes in [¹¹C]PIB uptake in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) over a long-term follow-up.

Methods

Six AD patients, ten MCI patients and eight healthy subjects underwent a [¹¹C]PIB PET scan at baseline and at 2 and 5 years. The clinical status of the MCI patients was evaluated every 6 months.

Results

The MCI group showed a significant increase in [¹¹C]PIB uptake over time (p?<?0.001), with a similar increase from baseline to 2 years (4.7 % per year) and from 2 to 5 years (5.0 % per year). Eight MCI patients (80 %) converted to AD, and two of these patients showed a normal [¹¹C]PIB scan at baseline but increased uptake later. There was an increase in [¹¹C]PIB uptake with time in the AD group (p?=?0.02), but this did not significantly differ from the change in the control group.

Conclusion

Our results revealed a significant increase in amyloid load even at the time of AD diagnosis in some of the MCI patients who converted. A positive [¹¹C]PIB scan at baseline in MCI patients strongly predicted future conversion to AD but a negative PIB scan in MCI patients did not exclude future conversion. The results suggest that there is wide individual variation in the brain amyloid load in MCI, and in the course of amyloid accumulation in relation to the clinical diagnosis of AD.

     

Imaging characteristic of dual-phase <Superscript>18</Superscript>F-florbetapir (AV-45/Amyvid) PET for the concomitant detection of perfusion deficits and beta-amyloid deposition in Alzheimer’s disease and mild cognitive impairment

Purpose

We investigated dual-phase ¹⁸F-florbetapir (AV-45/Amyvid) PET imaging for the concomitant detection of brain perfusion deficits and beta-amyloid deposition in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI), and in cognitively healthy controls (HCs).

Methods

A total of 82 subjects (24 AD patients, 44 MCI patients and 14 HCs) underwent both dual-phase ¹⁸F-AV-45 PET and MRI imaging. Dual-phase dynamic PET imaging consisted of (1) five 1-min scans obtained 1?–?6 min after tracer injection (perfusion ¹⁸F-AV-45 imaging, pAV-45), and (2) ten 1-min scans obtained 50?–?60 min after tracer injection (amyloid ¹⁸F-AV-45 imaging). Amyloid-negative MCI/AD patients were excluded. Volume of interest analysis and statistical parametric mapping of pAV-45 and ¹⁸F-AV-45 images were performed to investigate the perfusion deficits and the beta-amyloid burden in the three study groups. The associations between Mini-Mental State Examination (MMSE) scores and global perfusion deficits and amyloid deposition were investigated with linear and segmental linear correlation analyses.

Results

HCs generally had normal pAV-45 findings, whereas perfusion deficits were evident in the hippocampus, and temporal, parietal and middle frontal cortices in both MCI and AD patients. The motor-sensory cortex was relatively preserved. MMSE scores in the entire study cohort were significantly associated with the degree of perfusion impairment as assessed by pAV-45 imaging (r?=?0.5156, P?<?0.0001). ¹⁸F-AV-45 uptake was significantly higher in AD patients than in the two other study groups. However, the correlation between MMSE scores and ¹⁸F-AV-45 uptake in MCI patients was more of a binary phenomenon and began in MCI patients with MMSE score 23.14 when ¹⁸F-AV-45 uptake was higher and MMSE score lower than in patients with early MCI. Amyloid deposition started in the precuneus and the frontal and temporal regions in early MCI, ultimately reaching the maximum burden in advanced MCI.

Conclusion

Our results indicate that brain perfusion deficits and beta-amyloid deposition in AD follow different trajectories that can be successfully traced using dual-phase ¹⁸F-AV-45 PET imaging.

     

Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

Purpose

The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI).

Methods

We evaluated the supportive role of CSF Aβ₄₂, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression.

Results

Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer’s disease and in the differential diagnosis of non-Alzheimer’s disease dementias. The p-tau/Aβ₄₂ ratio was the only CSF biomarker providing a significant classification rate for Alzheimer’s disease. An Alzheimer’s disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer’s disease.

Conclusion

In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ₄₂ ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer’s disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.

     

Automated quantification of amyloid positron emission tomography: a comparison of PMOD and MIMneuro

Objective

The aim of this study was to examine and compare two automated quantitative software tools (PMOD and MIMneuro) for the quantification of amyloid positron emission tomography (PET).

Methods

A total of 30 subjects—15 Alzheimer’s disease (AD) patients and 15 cognitively normal age- and sex-matched controls—were enrolled. All subjects underwent structural volumetric magnetic resonance imaging (MRI) and amyloid PET scans with F-18 florbetaben. Regional standardized uptake value ratios (SUVRs) using the cerebellar cortex as a reference region were obtained using PMOD and MIMneuro.

Results

The SUVRs using both PMOD and MIMneuro showed high discriminatory power between the AD patients and cognitively normal controls. While PMOD and MIMneuro yielded significantly different SUVRs in some brain regions, the two methods had good overall agreement.

Conclusion

MIMneuro provides comparable performance to PMOD without the need to acquire brain MRI. Therefore, MIMneuro might be suitable for clinical use to determine amyloid positivity.

     

Head motion evaluation and correction for PET scans with 18F-FDG in the Japanese Alzheimer’s disease neuroimaging initiative (J-ADNI) multi-center study

Objective

Head motion during 30-min (six 5-min frames) brain PET scans starting 30 min post-injection of FDG was evaluated together with the effect of post hoc motion correction between frames in J-ADNI multicenter study carried out in 24 PET centers on a total of 172 subjects consisting of 81 normal subjects, 55 mild cognitive impairment (MCI) and 36 mild Alzheimer’s disease (AD) patients.

Methods

Based on the magnitude of the between-frame co-registration parameters, the scans were classified into six levels (A–F) of motion degree. The effect of motion and its correction was evaluated using between-frame variation of the regional FDG uptake values on ROIs placed over cerebral cortical areas.

Result

Although AD patients tended to present larger motion (motion level E or F in 22 % of the subjects) than MCI (3 %) and normal (4 %) subjects, unignorable motion was observed in a small number of subjects in the latter groups as well. The between-frame coefficient of variation (SD/mean) was 0.5 % in the frontal, 0.6 % in the parietal and 1.8 % in the posterior cingulate ROI for the scans of motion level 1. The respective values were 1.5, 1.4, and 3.6 % for the scans of motion level F, but reduced by the motion correction to 0.5, 0.4 and 0.8 %, respectively. The motion correction changed the ROI value for the posterior cingulate cortex by 11.6 % in the case of severest motion.

Conclusion

Substantial head motion occurs in a fraction of subjects in a multicenter setup which includes PET centers lacking sufficient experience in imaging demented patients. A simple frame-by-frame co-registration technique that can be applied to any PET camera model is effective in correcting for motion and improving quantitative capability.

     

Feasibility of FDG-PET in myocarditis: Comparison to CMR using integrated PET/MRI

Objective

Besides cardiac sarcoidosis, FDG-PET is rarely used in the diagnosis of myocardial inflammation, while cardiac MRI (CMR) is the actual imaging reference for the workup of myocarditis. Using integrated PET/MRI in patients with suspected myocarditis, we prospectively compared FDG-PET to CMR and the feasibility of integrated FDG-PET/MRI in myocarditis.

Methods

A total of 65 consecutive patients with suspected myocarditis were prospectively assessed using integrated cardiac FDG-PET/MRI. Studies comprised T2-weighted imaging, late gadolinium enhancement (LGE), and simultaneous PET acquisition. Physiological glucose uptake in the myocardium was suppressed using dietary preparation.

Results

FDG-PET/MRI was successful in 55 of 65 enrolled patients: two patients were excluded due to claustrophobia and eight patients due to failed inhibition of myocardial glucose uptake. Compared with CMR (LGE and/or T2), sensitivity and specificity of PET was 74% and 97%. Overall spatial agreement between PET and CMR was κ = 0.73. Spatial agreement between PET and T2 (κ = 0.75) was higher than agreement between PET and LGE (κ = 0.64) as well as between LGE and T2 (κ = 0.56).

Conclusion

In patients with suspected myocarditis, FDG-PET is in good agreement with CMR findings.

     

A new integrated dual time-point amyloid PET/MRI data analysis method

Purpose

In the initial evaluation of patients with suspected dementia and Alzheimer’s disease, there is no consensus on how to perform semiquantification of amyloid in such a way that it: (1) facilitates visual qualitative interpretation, (2) takes the kinetic behaviour of the tracer into consideration particularly with regard to at least partially correcting for blood flow dependence, (3) analyses the amyloid load based on accurate parcellation of cortical and subcortical areas, (4) includes partial volume effect correction (PVEC), (5) includes MRI-derived topographical indexes, (6) enables application to PET/MRI images and PET/CT images with separately acquired MR images, and (7) allows automation.

Methods

A method with all of these characteristics was retrospectively tested in 86 subjects who underwent amyloid (¹⁸F-florbetaben) PET/MRI in a clinical setting (using images acquired 90–110 min after injection, 53 were classified visually as amyloid-negative and 33 as amyloid-positive). Early images after tracer administration were acquired between 0 and 10 min after injection, and later images were acquired between 90 and 110 min after injection. PVEC of the PET data was carried out using the geometric transfer matrix method. Parametric images and some regional output parameters, including two innovative “dual time-point” indexes, were obtained.

Results

Subjects classified visually as amyloid-positive showed a sparse tracer uptake in the primary sensory, motor and visual areas in accordance with the isocortical stage of the topographic distribution of the amyloid plaque (Braak stages V/VI). In patients classified visually as amyloid-negative, the method revealed detectable levels of tracer uptake in the basal portions of the frontal and temporal lobes, areas that are known to be sites of early deposition of amyloid plaques that probably represented early accumulation (Braak stage A) that is typical of normal ageing. There was a strong correlation between age and the indexes of the new dual time-point amyloid imaging method in amyloid-negative patients.

Conclusions

The method can be considered a valuable tool in both routine clinical practice and in the research setting as it will standardize data regarding amyloid deposition. It could potentially also be used to identify early amyloid plaque deposition in younger subjects in whom treatment could theoretically be more effective.

     

<Superscript>18</Superscript>F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia

Objective

Recently, we developed a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-¹⁸F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (¹⁸F-FPYBF-2) (Ono et al., J Med Chem 54:2971–9, 2011). The aim of this study was to assess the feasibility of ¹⁸F-FPYBF-2 as an amyloid imaging PET tracer in a first clinical study with healthy volunteers and patients with various dementia and in comparative dual tracer study using ¹¹C-Pittsburgh Compound B (¹¹C-PiB).

Methods

61 healthy volunteers (age: 53.7?±?13.1 years old; 19 male and 42 female; age range 24–79) and 55 patients with suspected dementia [Alzheimer’s Disease (AD); early AD: n?=?19 and moderate stage AD: n?=?8, other dementia: n?=?9, mild cognitive impairment (MCI): n?=?16, cognitively normal: n?=?3] for first clinical study underwent static head PET/CT scan using ¹⁸ F ^? FPYBF-2 at 50–70 min after injection. 13 volunteers and 14 patients also underwent dynamic PET scan at 0–50 min at the same instant. 16 subjects (volunteers: n?=?5, patients with dementia: n?=?11) (age: 66.3?±?14.2 years old; 10 males and 6 females) were evaluated for comparative study (50–70 min after injection) using ¹⁸F-FPYBF-2 and ¹¹C-PiB on separate days, respectively. Quantitative analysis of mean cortical uptake was calculated using Mean Cortical Index of SUVR (standardized uptake value ratio) based on the established method for ¹¹C-PiB analysis using cerebellar cortex as control.

Results

Studies with healthy volunteers showed that ¹⁸F-FPYBF-2 uptake was mainly observed in cerebral white matter and that average Mean Cortical Index at 50–70 min was low and stable (1.066?±?0.069) basically independent from age or gender. In patients with AD, ¹⁸F-FPYBF-2 uptake was observed both in cerebral white and gray matter, and Mean Cortical Index was significantly higher (early AD: 1.288?±?0.134, moderate AD: 1.342?±?0.191) than those of volunteers and other dementia (1.018?±?0.057). In comparative study, the results of ¹⁸F-FPYBF-2 PET/CT were comparable with those of ¹¹C-PiB, and the Mean Cortical Index (¹⁸F-FPYBF-2: 1.173?±?0.215; ¹¹C-PiB: 1.435?±?0.474) showed direct proportional relationship with each other (p?<?0.0001).

Conclusions

Our first clinical study suggest that ¹⁸F-FPYBF-2 is a useful PET tracer for the evaluation of β-amyloid deposition and that quantitative analysis of Mean Cortical Index of SUVR is a reliable diagnostic tool for the diagnosis of AD.

     

Simultaneous whole-body and breast 18F-FDG PET/MRI examinations in patients with breast cancer: a comparison of apparent diffusion coefficients and maximum standardized uptake values

Purpose

To compare standardized uptake value (SUV) and apparent diffusion coefficient (ADC) values acquired using a PET/MRI scanner in breast cancer patients.

Materials and methods

Whole-body PET/MRI and breast PET/MRI were performed in 108 consecutive patients. Ninety-four patients who had a total of 100 breast cancers were analyzed. SUVmax and ADCmean acquired using breast PET/MRI were compared with pathologic prognostic factors.

Results

All the lesions were visually detectable using PET and diffusion-weighted imaging (DWI) on breast PET/MRI; however, lesions were visually undetectable on whole-body DWI in 13 patients (13%) or on whole-body PET in 7 patients (7%). An analysis of ADCmean and SUVmax demonstrated a statistically significant correlation between whole-body imaging and breast imaging (rho = 0.613, p < 0.001 and rho = 0.928, p < 0.001, respectively). In a univariate analysis, SUVmax was significantly correlated with HER2 status (p < 0.001), Ki-67 (p = 0.014), tumor size (p = 0.0177), and nuclear grade (p = 0.0448). In multiple regression analysis, only tumor size (p = 0.00701) was shown to independently influence SUVmax.

Conclusion

Prone breast imaging was more sensitive than whole-body PET/MRI for detection of breast cancers. Both SUVmax and ADCmean showed limited correlation with pathologic prognostic factors.

     

Comparison between MRI-based attenuation correction methods for brain PET in dementia patients

Introduction

The combination of Positron Emission Tomography (PET) with magnetic resonance imaging (MRI) in hybrid PET/MRI scanners offers a number of advantages in investigating brain structure and function. A critical step of PET data reconstruction is attenuation correction (AC). Accounting for bone in attenuation maps (μ-map) was shown to be important in brain PET studies. While there are a number of MRI-based AC methods, no systematic comparison between them has been performed so far. The aim of this work was to study the different performance obtained by some of the recent methods presented in the literature. To perform such a comparison, we focused on [¹⁸F]-Fluorodeoxyglucose-PET/MRI neurodegenerative dementing disorders, which are known to exhibit reduced levels of glucose metabolism in certain brain regions.

Methods

Four novel methods were used to calculate μ-maps from MRI data of 15 patients with Alzheimer’s dementia (AD). The methods cover two atlas-based methods, a segmentation method, and a hybrid template/segmentation method. Additionally, the Dixon-based and a UTE-based method, offered by a vendor, were included in the comparison. Performance was assessed at three levels: tissue identification accuracy in the μ-map, quantitative accuracy of reconstructed PET data in specific brain regions, and precision in diagnostic images at identifying hypometabolic areas.

Results

Quantitative regional errors of ?20–?10 % were obtained using the vendor’s AC methods, whereas the novel methods produced errors in a margin of ±5 %. The obtained precision at identifying areas with abnormally low levels of glucose uptake, potentially regions affected by AD, were 62.9 and 79.5 % for the two vendor AC methods, the former ignoring bone and the latter including bone information. The precision increased to 87.5–93.3 % in average for the four new methods, exhibiting similar performances.

Conclusion

We confirm that the AC methods based on the Dixon and UTE sequences provided by the vendor are inferior to alternative techniques. As a novel finding, there was no substantial difference between the recently proposed atlas-based, template-based and segmentation-based methods.

     

Comparison of the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo)

Purpose

To compare the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo).

Methods

MoCo PET/DCE-MRI of the upper abdomen was acquired in 44 consecutive oncologic patients and compared with non-MoCo PET/MRI. SUVmax and MTV of FDG-avid upper abdominal malignant lesions were assessed on MoCo and non-MoCo PET images. Image quality was compared between MoCo DCE-MRI and non-MoCo CE-MRI, and between fused MoCo PET/MRI and fused non-MoCo PET/MRI images.

Results

MoCo PET resulted in higher SUVmax (10.8?±?5.45) than non-MoCo PET (9.62?±?5.42) and lower MTV (35.55?±?141.95 cm³) than non-MoCo PET (38.11?±?198.14 cm³; p?<?0.005 for both). The quality of MoCo DCE-MRI images (4.73?±?0.5) was higher than that of non-MoCo CE-MRI images (4.53±0.71; p?=?0.037). The quality of fused MoCo-PET/MRI images (4.96?±?0.16) was higher than that of fused non-MoCo PET/MRI images (4.39?±?0.66; p?<?0.005).

Conclusion

MoCo PET/MRI provided qualitatively better images than non-MoCo PET/MRI, and upper abdominal malignant lesions demonstrated higher SUVmax and lower MTV on MoCo PET/MRI.

     

Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: <Superscript>18</Superscript>F-florbetapir (AV-45/Amyvid) PET study

Purpose

The objective of this study was to evaluate the amyloid burden, as assessed by ¹⁸F-florbetapir (AV-45/Amyvid) positron emission tomography PET, in patients with major depressive disorder (MDD) with different subtypes of mild cognitive impairment (MCI) and the relationship between amyloid burden and cognition in MDD patients.

Methods

The study included 55 MDD patients without dementia and 21 healthy control subjects (HCs) who were assessed using a comprehensive cognitive test battery and ¹⁸F-florbetapir PET imaging. The standardized uptake value ratios (SUVR) in eight cortical regions using the whole cerebellum as reference region were determined and voxel-wise comparisons between the HC and MDD groups were performed. Vascular risk factors, serum homocysteine level and the apolipoprotein E (ApoE) genotype were also determined.

Results

Among the 55 MDD patients, 22 (40.0 %) had MCI, 12 (21.8 %) non-amnestic MCI (naMCI) and 10 (18.2 %) amnestic MCI (aMCI). The MDD patients with aMCI had the highest relative ¹⁸F-florbetapir uptake in all cortical regions, and a significant difference in relative ¹⁸F-florbetapir uptake was found in the parietal region as compared with that in naMCI subjects (P?<?0.05) and HCs (P?<?0.01). Voxel-wise analyses revealed significantly increased relative ¹⁸F-florbetapir uptake in the MDD patients with aMCI and naMCI in the frontal, parietal, temporal and occipital areas (P?<?0.005). The global cortical SUVR was significantly negatively correlated with MMSE score (r?=??0.342, P?=?0.010) and memory function (r?=??0.328, P?=?0.015). The negative correlation between the global SUVR and memory in the MDD patients remained significant in multiple regression analyses that included age, educational level, ApoE genotype, and depression severity (β?=??3.607, t?=??2.874, P?=?0.006).

Conclusion

We found preliminary evidence of brain beta-amyloid deposition in MDD patients with different subtypes of MCI. Our findings in MDD patients support the hypothesis that a higher amyloid burden is associated with a poorer memory performance. We also observed a high prevalence of MCI among elderly depressed patients, and depressed patients with MCI exhibited heterogeneously elevated ¹⁸F-florbetapir retention as compared with depressed patients without MCI. The higher amyloid burden in the aMCI patients suggests that these patients may also be more likely to develop Alzheimer’s disease than other patients diagnosed with major depression.

     

Simultaneous whole-body <Superscript>18</Superscript>F–PSMA-1007-PET/MRI with integrated high-resolution multiparametric imaging of the prostatic fossa for comprehensive oncological staging of patients with prostate cancer: a pilot study

Introduction

The aim of the present study was to explore the clinical feasibility and reproducibility of a comprehensive whole-body ¹⁸F–PSMA-1007-PET/MRI protocol for imaging prostate cancer (PC) patients.

Methods

Eight patients with high-risk biopsy-proven PC underwent a whole-body PET/MRI (3 h p.i.) including a multi-parametric prostate MRI after ¹⁸F–PSMA-1007-PET/CT (1 h p.i.) which served as reference. Seven patients presented with non-treated PC, whereas one patient presented with biochemical recurrence. SUV_mean-quantification was performed using a 3D–isocontour volume-of-interest. Imaging data was consulted for TNM-staging and compared with histopathology. PC was confirmed in 4/7 patients additionally by histopathology after surgery. PET-artifacts, co-registration of pelvic PET/MRI and MRI-data were assessed (PI-RADS 2.0).

Results

The examinations were well accepted by patients and comprised 1 h. SUV_mean-values between PET/CT (1 h p.i.) and PET/MRI (3 h p.i.) were significantly correlated (p < 0.0001, respectively) and similar to literature of ¹⁸F–PSMA-1007-PET/CT 1 h vs 3 h p.i. The dominant intraprostatic lesion could be detected in all seven patients in both PET and MRI. T2c, T3a, T3b and T4 features were detected complimentarily by PET and MRI in five patients. PET/MRI demonstrated moderate photopenic PET-artifacts surrounding liver and kidneys representing high-contrast areas, no PET-artifacts were observed for PET/CT. Simultaneous PET-readout during prostate MRI achieved optimal co-registration results.

Conclusions

The presented ¹⁸F–PSMA-1007-PET/MRI protocol combines efficient whole-body assessment with high-resolution co-registered PET/MRI of the prostatic fossa for comprehensive oncological staging of patients with PC.

     

Hybrid <Superscript>18</Superscript>F–FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

Purpose

Our purpose in this study was to assess the added clinical value of hybrid ¹⁸F–FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).

Methods

In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed.

Results

A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed.

Conclusion

Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients.

     

18F–FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage

Purpose

We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer’s disease (MCI-AD).

Methods

We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F–fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia.

Results

Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007).

Conclusion

The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal metabolism captures speed of conversion to dementia in MCI-AD since baseline. The highlighted prognostic pattern is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).

     

Value of FDG-PET scans of non-demented patients in predicting rates of future cognitive and functional decline

Purpose

The aim of this study was to examine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting subsequent rates of functional and cognitive decline among subjects considered cognitively normal (CN) or clinically diagnosed with mild cognitive impairment (MCI).

Methods

Analyses of 276 subjects, 92 CN subjects and 184 with MCI, who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative, were conducted. Functional decline was assessed using scores on the Functional Activities Questionnaire (FAQ) obtained over a period of 36 months, while cognitive decline was determined using the Alzheimer’s disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) scores. PET images were analyzed using clinically routine brain quantification software. A dementia prognosis index (DPI), derived from a ratio of uptake values in regions of interest known to be hypometabolic in Alzheimer’s disease to regions known to be stable, was generated for each baseline FDG-PET scan. The DPI was correlated with change in scores on the neuropsychological examinations to examine the predictive value of baseline FDG-PET.

Results

DPI powerfully predicted rate of functional decline among MCI patients (t = 5.75, p?<?1.0E-8) and pooled N?+?MCI patient groups (t?=?7.02, p?<?1.0E-11). Rate of cognitive decline on MMSE was also predicted by the DPI among MCI (t?=?6.96, p?<?1.0E-10) and pooled N?+?MCI (t?=?8.78, p?<?5.0E-16). Rate of cognitive decline on ADAS-cog was powerfully predicted by the DPI alone among N (p?<?0.001), MCI (t?=?6.46, p?<?1.0E-9) and for pooled N?+?MCI (t?=?8.85, p?=?1.1E-16).

Conclusions

These findings suggest that an index, derivable from automated regional analysis of brain PET scans, can be used to help predict rates of functional and cognitive deterioration in the years following baseline PET.

     

Prospective evaluation of <Superscript>18</Superscript>F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial)

Purpose

The purpose of this study was to evaluate ¹⁸F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa).

Methods

Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq ¹⁸F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV_max) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V_T). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455.

Results

In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV_max and V_T of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes.

Conclusions

Quantitative ¹⁸F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. ¹⁸F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.

     

Early [<Superscript>18</Superscript>F]florbetaben and [<Superscript>11</Superscript>C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer’s disease

Purpose

[¹⁸F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [¹¹C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [¹⁸F]FDG uptake. Uptake data for ¹⁸F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [¹⁸F]FBB in the diagnosis of Alzhimers disease (AD).

Methods

This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [¹¹C]PiB (11 patients) or [¹⁸F]FBB (11 patients) in routine clinical practice. Images were acquired 1 – 9 min after administration of both tracers and 40 – 70 min and 90 – 110 min after administration of [¹¹C]PiB and [¹⁸F]FBB, respectively. The patients also underwent [¹⁸F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated.

Results

Regional visual scores of early Aβ tracer and [¹⁸F]FDG PET images were significantly correlated (Spearman’s ρ?=?0.780, P?<?0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [¹⁸F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [¹⁸F]FDG data (r?=?0.779, P?<?0.001), but there were no differences between [¹⁸F]FBB and [¹¹C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [¹⁸F]FDG PET images were correlated with MMSE scores (ρ?=?0.458, P?=?0.032, and ρ?=?0.456, P?=?0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [¹⁸F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison.

Conclusion

Early [¹⁸F]FBB and [¹¹C]PiB PET brain images are similar to [¹⁸F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [¹⁸F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.