The diagnosis of a parkinsonian syndrome based on clinical criteria remains sometimes difficult, especially at disease onset. Brain or heart molecular imaging techniques (SPECT or PET) can provide a ...major help to improve and speed up diagnosis, influencing treatment strategies. Presynaptic dopaminergic imaging using either 18F-Dopa PET or 123I -2β-Carbomethoxy-3β-(4-Iodophenyl)- N-(3-Fluoropropyl) Nortropane (123I-Ioflupane)SPECT demonstrates or rules out the presence of a dopaminergic degenerative process. This allows to distinguish Parkinson's disease, Parkinson “plus” syndromes and dementia with Lewy bodies (reduced radiotracers binding) from essential tremor, psychogenic, post-neuroleptic or vascular parkinsonisms, dopa-responsive dystonia and Alzheimer's disease (normal radiotracers binding). For differential diagnosis between Parkinson's disease and Parkinson “plus” syndromes, brain molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET or 99mTc-HMPAO SPECT can provide useful information, whereas 18F-Dopa PET or 123I-Ioflupane does not separate these entities. Finally, sympathetic cardiac 123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy or SPECT can help distinguishing Parkinson's disease and dementia with Lew bodies (decreased binding) from multiple system atrophy and progressive supranuclear palsy (normal binding). New radiotracers notably those targeting the pathological process itself such as Tau aggregates are under development and may provide interesting informations to delineate the different Parkinson “plus” syndromes.
•18F-Dopa PET/123I-Ioflupane assesses dopaminergic degeneration.•18F-Dopa PET/123I-Ioflupane SPECT do not distinguish PD from Parkinson “Plus”.•18F-FDG PET separates PD from Parkinson “Plus”.•123 I-MIBG SPECT help distinguishing PD and DLB from MSA/PSP.
•Enlarged lateral ventricles heavily affect the spatial normalization performance.•Suitable CT-guided normalization for brains with enlarged lateral ventricles.•CT-guided normalization of SPECT is a ...reliable method for quantitative studies.•Less biased SPECT quantification in caudate thanks to normalization improvement.
Spatial normalization is a prerequisite step for the quantitative analysis of SPECT or PET brain images using volume-of-interest (VOI) template or voxel-based analysis. MRI-guided spatial normalization is the gold standard, but the wide use of PET/CT or SPECT/CT in routine clinical practice makes CT-guided spatial normalization a necessary alternative. Ventricular enlargement is observed with aging, and it hampers the spatial normalization of the lateral ventricles and striatal regions, limiting their analysis. The aim of the present study was to propose a robust spatial normalization method based on CT scans that takes into account features of the aging brain to reduce bias in the CT-guided striatal analysis of SPECT images.
We propose an enhanced CT-guided spatial normalization pipeline based on SPM12. Performance of the proposed pipeline was assessed on visually normal 123I-FP-CIT SPECT/CT images. SPM12 default CT-guided spatial normalization was used as reference method. The metrics assessed were the overlap between the spatially normalized lateral ventricles and caudate/putamen VOIs, and the computation of caudate and putamen specific binding ratios (SBR).
In total 231 subjects (mean age ± SD = 61.9 ± 15.5 years) were included in the statistical analysis. The mean overlap between the spatially normalized lateral ventricles of subjects and the caudate VOI and the mean SBR of caudate were respectively 38.40 % (± SD = 19.48 %) of the VOI and 1.77 (± 0.79) when performing SPM12 default spatial normalization. The mean overlap decreased to 9.13 % (± SD = 1.41 %, P < 0.001) of the VOI and the SBR of caudate increased to 2.38 (± 0.51, P < 0.0001) when performing the proposed pipeline. Spatially normalized lateral ventricles did not overlap with putamen VOI using either method. The mean putamen SBR value derived from the proposed spatial normalization (2.75 ± 0.54) was not significantly different from that derived from the default SPM12 spatial normalization (2.83 ± 0.52, P > 0.05).
The automatic CT-guided spatial normalization used herein led to a less biased spatial normalization of SPECT images, hence an improved semi-quantitative analysis. The proposed pipeline could be implemented in clinical routine to perform a more robust SBR computation using hybrid imaging.
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Background
To show the equivalence between the specific binding ratios (SBR) of visually normal
123
I-FP-CIT SPECT scans from patients to those from healthy volunteers (Hv) or patients without ...dopaminergic degeneration to allow their use as a reference database.
Methods
The SBR values of visually normal SPECT scans from 3 groups were studied: (1) suspected Parkinsonism and no diagnostic follow-up (ScanOnlyDB:
n
= 764, NM/CT 670 CZT, GE Healthcare), (2) no degenerative dopaminergic pathology after a 5-year follow-up (NoDG5YearsDB:
n
= 237, Symbia T2, Siemens Medical Solutions), and 3) Hv (HvDB:
n
= 118, commercial GE database). A general linear model (GLM) was constructed with caudate, putamen, and striatum SBR as the dependent variables, and age and gender as the independent variables. Following post-reconstruction harmonization of the data, DB were combined in pairs, ScanOnlyDB&NoDG5yearsDG and ScanOnlyDB&HvDB before performing GLM analysis. Additionally, ScanOnlyDB GLM estimates were compared to those published from Siemens commercial DB (SiemensDB) and ENC-DAT.
Results
The dispersion parameters,
R
2
and the SBR coefficients of variation, did not differ between databases. For all volumes of interest and all databases, SBR decreased significantly with age (e.g., decrease per decade for the striatum: − 4.94% for ScanOnlyDB, − 4.65% for NoDG5YearsDB, − 5.69% for HvDB). There was a significant covariance between SBR and gender for ScanOnlyDB (
P
< 10
–5
) and NoDG5YearsDB (
P
< 10
–2
). The age-gender interaction was significant only for ScanOnlyDB (
P
< 10
–2
), and the p-value decreased to 10
–6
after combining ScanOnlyDB with NoDG5YearsDB. ScanOnlyDB GLM estimates were not significantly different from those from SiemensDB or ENC-DAT except for age-gender interaction.
Conclusion
SBR values distribution from visually normal scans were not different from the existing reference database, enabling this method to create a reference database by expert nuclear physicians. In addition, it showed a rarely described age-gender interaction related to its size. The proposed post-reconstruction harmonization method can also facilitate the use of semi-quantitative analysis.
A number of results emphasize autoimmune characteristics in psychiatric diseases, including Affective (AF) and Schizophrenic (SZ) Spectrum Disorders.
In this study, serum/plasma samples of n=34 AF ...(ICD-10 F30-F33) and n=47 SZ (ICD-10 F20-F25) patients, as well as n=10 healthy controls (HDs), were tested for autoantibodies directed against cytokines and different Type I, Type II and Type III interferons using Luminex® technology.
Significant amounts of autoantibodies against cytokines were found. Specifically, IFN- λ (AF n=4, SZ n=4), IFN- ω (AF n=2, SZ n=3), and TNF-α (AF n=4, SZ n=1) were selectively increased.
The results support autoimmune dysregulation as a contributing factor in psychiatric diseases. Interestingly, the detected patterns were not different between AF and SZ patients. The humoral immunity against common virus infections such as EBV, CMV, HSV-1 and HHV-6 is currently tested.
Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of ...RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6 months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6 months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension.
Affective (AF) and Schizophrenic (SZ) Spectrum disorders manifest with risk factors, involving inflammatory processes linked to infections and autoimmunity. This study searched for novel biomarkers ...in cerebrospinal fluid (CSF) and peripheral blood. A total of 29 AF and 39 SZ patients with treatment-resistant disease were included. In CSF, the chemokine IL-8 was significantly elevated in AF and SZ patients. IL-8 promotes chemotaxis by neutrophils and may originate from different tissues. S100B, a glia-derived brain damage marker, was higher in CSF from AF than SZ patients. Among the plasma-derived biomarkers, ferritin was elevated in AF and SZ. Soluble CD25, indicating T
dysfunction, was higher in SZ than in AF patients. Interferon-γ, implying virus-specific immune activation, was positive in selective AF patients, only. Both groups showed elevated expression of immunosuppressive CD33 on monocytes, but higher amounts of CD123
plasmacytoid dendritic cells were restricted to SZ. In conclusion, chemotactic IL-8 indicates neuronal stress and inflammation in the CSF of both groups. Novel plasma-derived biomarkers such as sCD25 and monocytic CD33 distinguish SZ from AF with an autoimmune phenotype.
PURPOSEThe aim of this study was to determine the minimum acquisition time without decreasing lesion detectability of bone SPECT using a whole-body cadmium-zinc-telluride camera.
METHODSPatients ...referred for bone SPECT were retrospectively included. SPECT of 30 patients were reframed from native data (16 s/projection) to produce 10-, 5-, and 3-s/projection data sets. A “critical” acquisition time/projection was defined as that below which the SPECT quality becomes insufficient for interpretation, as determined by 3 reviewers using a 4-point scale (0 = quality insufficient for interpretation, 1 = average, 2 = good, 3 = excellent). Three reviewers (blinded to the acquisition time) evaluated SPECT data sets (n = 79), native and reframed with “critical” acquisition times, in a randomized order. A lesion was defined as any uptake considered pathological by a reviewer. Lesion detectability equivalence between native SPECT and reframed SPECT was assessed by calculating a coefficient (κ) for each reviewer.
RESULTSImage quality of the first sample (n = 30) was significantly and progressively less well graded for the reframed data sets by all reviewers. Only 1 patient was graded 0 by each reviewer for the 5-s/projection data set. For the 3-s/projection data set, 3 patients were graded 0. No patients were graded 0 for 10-s/projection data set. The minimal acquisition time, for each projection, was defined as 5 s/projection. The coefficient κ, between native and reframed, with critical acquisition time/projection SPECT was greater than 0.9 for each reviewer.
CONCLUSIONSThe more contrasted images of the cadmium-zinc-telluride camera allow performance of 5-s/projection SPECT without loss of lesion detectability. This suggests the possibility of performing whole-body SPECT in a reasonable time or reducing injected doses, especially in pediatric patients.
Inflammatory macrophages in patients with fatigue Schneider, E. Marion; Schneider, Julian M.; Scheiber, Christian ...
Journal of affective disorders reports,
April 2023, 2023-04-00, 2023-04-01, Letnik:
12
Journal Article
Recenzirano
Odprti dostop
Hyperinflammatory, so-called M1 macrophages play a major role in chronic inflammatory diseases often linked to impaired well-being as well as fatigue and sarkopenia. Cytokines such as IL-1, IL-6 play ...a role in polarizing the differentiation into M1 macrophages and simultanously inhibit the differentiation of anti-inflammatory M2 macrophages.
We enriched blood derived macrophages from peripheral blood and characterized their phenotypes by flow cytometry. The purinergic receptor P2 × 7 was tested by patch clamping and ion flux measurement. Microparticle and exosome release was induced by exogenous ATP-stimulation and qualified by trans-electorn microscopy as well as by nanosizer measurements.
M1 macrophages typically lacked surface CD163 and P2 × 7, but M2 macrophages expressed both markers. ATP stimulation induced cell death in M1 but microparticle and exosome release in M2 macrophages. Ion channel measurement confirmed the hypersensitivity of M1 and impaired ion flux by ATP. These result imply that chronic inflammatory diseases linked to highly elevated M1 type macrophages are highly sensitive to exogenous ATP, the most important danger signal in physical and psychiatric trauma. By contrast, anti-inflammatory, M2 macrophages mediate Calcium-signaling and exosome release upon ATP stimulation. MiRNA expression analysis further demonstrated that Let7b-5p discriminates between M1 and M2 macrophage polarization.
M1 macrophage and microglia polarization may explain the detrimental response against ATP related trauma in a number of inflammatory conditions which may fuel into fatigue and sarkopenia.
Virus-associated chronic inflammation may contribute to autoimmunity in a number of diseases. In the brain, autoimmune encephalitis appears related to fluctuating reactivation states of neurotropic ...viruses. In addition, viral miRNAs and proteins can be transmitted via exosomes, which constitute novel but highly relevant mediators of cellular communication. The current study questioned the role of HSV-1-encoded and host-derived miRNAs in cerebrospinal fluid (CSF)-derived exosomes, enriched from stress-induced neuroinflammatory diseases, mainly subarachnoid hemorrhage (SAH), psychiatric disorders (AF and SZ), and various other neuroinflammatory diseases. The results were compared with CSF exosomes from control donors devoid of any neuroinflammatory pathology. Serology proved positive, but variable immunity against herpesviruses in the majority of patients, except controls. Selective ultrastructural examinations identified distinct, herpesvirus-like particles in CSF-derived lymphocytes and monocytes. The likely release of extracellular vesicles and exosomes was most frequently observed from CSF monocytes. The exosomes released were structurally similar to highly purified stem-cell-derived exosomes. Exosomal RNA was quantified for HSV-1-derived miR-H2-3p, miR-H3-3p, miR-H4-3p, miR-H4-5p, miR-H6-3p, miR-H27 and host-derived miR-21-5p, miR-146a-5p, miR-155-5p, and miR-138-5p and correlated with the oxidative stress chemokine IL-8 and the axonal damage marker neurofilament light chain (NfL). Replication-associated miR-H27 correlated with neuronal damage marker NfL, and cell-derived miR-155-5p correlated with oxidative stress marker IL-8. Elevated miR-138-5p targeting HSV-1 latency-associated ICP0 inversely correlated with lower HSV-1 antibodies in CSF. In summary, miR-H27 and miR-155-5p may constitute neuroinflammatory markers for delineating frequent and fluctuating HSV-1 replication and NfL-related axonal damage in addition to the oxidative stress cytokine IL-8 in the brain. Tentatively, HSV-1 remains a relevant pathogen conditioning autoimmune processes and a psychiatric clinical phenotype.
Purpose
Iodine 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-
N
-(3-fluoropropyl) nortropane (
123
I-FP-CIT) SPECT can be performed to distinguish degenerative forms of movement ...disorders/parkinsonism/tremor from other entities such as idiopathic tremor or drug-induced parkinsonism. For equivocal cases, semi-quantification and comparison to reference values are a necessary addition to visual interpretation of
123
I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated
123
I-FP-CIT reference values from individuals with various neurological conditions but without dopaminergic degeneration, scanned at a single center on the same SPECT-CT system following the same protocol, and compared them to references from a multi-center database built using healthy volunteers’ data.
Methods
From a cohort of 1884 patients, we identified 237 subjects (120 men, 117 women, age range 16–88 years) through a two-stage selection process. Every patient had a final clinical diagnosis after a mean follow-up of 4.8 ± 1.3 years. Images were reconstructed using (1) Flash3D with scatter and CT-based attenuation corrections (AC) and (2) filtered back projection with Chang AC. Volume-of-interest analysis was performed using a commercial software to calculate specific binding ratios (SBRs), caudate-to-putamen ratios, and asymmetry values on different striatal regions. Generated reference values were assessed according to age and gender and compared with those from the ENC-DAT study, and their robustness was tested against a cohort of patients with different diagnoses.
Results
Age had a significant negative linear effect on all SBRs. Overall, the reduction rate per decade in SBR was between 3.80 and 5.70%. Women had greater SBRs than men, but this gender difference was only statistically significant for the Flash3D database. Linear regression was used to correct for age-dependency of SBRs and to allow comparisons to age-matched reference values and “normality” limits. Generated regression parameters and their 95% confidence intervals (CIs) were comparable to corresponding European Normal Control Database of DaTscan (ENC-DAT) results. For example, 95% CI mean slope for the striatum in women is − 0.015 (− 0.019, − 0.011) for the Flash3D database versus − 0.015 (− 0.021, − 0.009) for ENC-DAT. Caudate-to-putamen ratios and asymmetries were not influenced by age or gender.
Conclusion
The generated
123
I-FP-CIT references values have similar age-related distribution, with no increase in variance due to comorbidities when compared to values from a multi-center study with healthy volunteers. This makes it possible for sites to build their
123
I-FP-CIT references from scans acquired during routine clinical practice.
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