Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease.

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-ß deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker.

Diagnosing Lung Nodules on Oncologic MR/PET Imaging: Comparison of Fast T1-Weighted Sequences and Influence of Image Acquisition in Inspiration and Expiration Breath-Hold.

OBJECTIVE: First, to investigate the diagnostic performance of fast T1-weighted sequences for lung nodule evaluation in oncologic magnetic resonance (MR)/positron emission tomography (PET). Second, to evaluate the influence of image acquisition in inspiration and expiration breath-hold on diagnostic performance. MATERIALS AND METHODS: The study was approved by the local Institutional Review Board. PET/CT and MR/PET of 44 cancer patients were evaluated by 2 readers. PET/CT included lung computed tomography (CT) scans in inspiration and expiration (CTin, CTex). MR/PET included Dixon sequence for attenuation correction and fast T1-weighted volumetric interpolated breath-hold examination (VIBE) sequences (volume interpolated breath-hold examination acquired in inspiration [VIBEin], volume interpolated breath-hold examination acquired in expiration [VIBEex]). Diagnostic performance was analyzed for lesion-, lobe-, and size-dependence. Diagnostic confidence was evaluated (4-point Likert-scale; 1 = high). Jackknife alternative free-response receiver-operating characteristic (JAFROC) analysis was performed. RESULTS: Seventy-six pulmonary lesions were evaluated. Lesion-based detection rates were: CTex, 77.6%; VIBEin, 53.3%; VIBEex, 51.3%; and Dixon, 22.4%. Lobe-based detection rates were: CTex, 89.6%; VIBEin, 58.3%; VIBEex, 60.4%; and Dixon, 31.3%. In contrast to CT, inspiration versus expiration did not alter diagnostic performance in VIBE sequences. Diagnostic confidence was best for VIBEin and CTex and decreased in VIBEex and Dixon (1.2 ± 0.6; 1.2 ± 0.7; 1.5 ± 0.9; 1.7 ± 1.1, respectively). The JAFROC figure-of-merit of Dixon was significantly lower. All patients with malignant lesions were identified by CTex, VIBEin, and VIBEex, while 3 patients were false-negative in Dixon. CONCLUSION: Fast T1-weighted VIBE sequences allow for identification of patients with malignant pulmonary lesions. The Dixon sequence is not recommended for lung nodule evaluation in oncologic MR/PET patients. In contrast to CT, inspiration versus expiratory breath-hold in VIBE sequences was less crucial for lung nodule evaluation but was important for diagnostic confidence.

Comparison of Tc-99m sestamibi SPECT with fractional flow reserve in patients with intermediate coronary artery stenoses.

BACKGROUND: Myocardial single photon emission computed tomography (SPECT) is an established noninvasive method for the assessment of the functional significance of coronary artery stenoses. Intracoronary pressure measurements to determine fractional flow reserve (FFR) are increasingly performed during coronary angiography whenever an immediate decision regarding possible intervention is required. We hypothesized that the regional summed difference score (SDSr), reflecting reversible perfusion defects in the myocardial supply area of the FFR target vessel, would be the best predictor of an abnormal FFR in patients without prior myocardial infarction. Otherwise, a regional summed stress score (SSSr) should be the best predictor of an abnormal FFR in patients with prior myocardial infarction for different patient subgroups with coronary artery disease. METHODS AND RESULTS: In this study 50 patients (mean age, 65 +/- 9.1 years; 18 women) with coronary artery disease and a 50% to 75% coronary stenosis (target vessel) were prospectively investigated. Dobutamine myocardial SPECT was performed as a single-day stress/rest protocol by use of technetium 99m sestamibi. For image interpretation, semiquantitative analysis was conducted by calculating SSSr and SDSr. Within 8 (+/-14.9) days, coronary angiography was performed and FFR was calculated by use of a pressure wire (normal FFR, > or = 0.75). The mean FFR of all patients was 0.78 +/- 0.14. Of 50 patients, 17 had an FFR lower than 0.75 in the target vessel. Receiver operating characteristic analysis identified an SDSr of 1 or greater and an SSSr of 3 or greater as the best threshold values for predicting ischemic FFR. Sensitivity, specificity, and negative and positive predictive values of SDSr and SSSr for the detection of FFR values lower than 0.75 in the target vessel were 80%, 76%, 53%, and 92%, respectively, and 70%, 93%, 78%, and 90%, respectively, in patients without prior myocardial infarction and 57%, 50%, 67%, and 40%, respectively, and 100%, 50%, 78%, and 100%, respectively, in patients with prior myocardial infarction. Weak correlation was found between the single values of FFR with both SDSr and SSSr for the different patient subgroups. CONCLUSION: Among the dobutamine myocardial scintigraphy variables studied, SDSr was the best predictor of an abnormal FFR (cutoff value of 0.75) in patients without prior myocardial infarction. As assumed, SSSr was the best predictor of an abnormal FFR in patients with prior myocardial infarction in the target region.