CT-guided spatial normalization of nuclear hybrid imaging adapted to enlarged ventricles: Impact on striatal uptake quantification.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

PURPOSE: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results. PATIENTS AND METHODS: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification. RESULTS: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15). CONCLUSIONS: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients.

BACKGROUND: To show the equivalence between the specific binding ratios (SBR) of visually normal 123I-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, R2 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.

Old and New Biomarkers for Infection, Inflammation, and Autoimmunity in Treatment-Resistant Affective and Schizophrenic Spectrum Disorders.

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 Treg 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.

Single-site 123I-FP-CIT reference values from individuals with non-degenerative parkinsonism-comparison with values from healthy volunteers.

PURPOSE: Iodine 123-radiolabeled 2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-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 123I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated 123I-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 123I-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 123I-FP-CIT references from scans acquired during routine clinical practice.

Reduced Scan Time in 123I-FP-CIT SPECT Imaging Using a Large-Field Cadmium-Zinc-Telluride Camera.

We evaluated the reproducibility of I-ioflupane (I-FP-CIT) SPECT with shorter scan times using a CZT camera. One hundred ninety-nine I-FP-CIT SPECT scans obtained with standard scan time (30 minutes) were truncated to provide 24-, 18-, and 15-minute study simulations. Striatal binding ratios were automatically calculated and remained stable for all series. At 15 minutes, only 10 of 398 striata (2.5%) showed statistically significant different striatal binding ratios compared with reference series. These series were reviewed by 2 operators, and a perfect agreement was found for each patient. Therefore, CZT camera allows a 2-fold scan time reduction in I-FP-CIT SPECT.

What a neurologist should know about PET and SPECT functional imaging for parkinsonism: A practical perspective.

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 -2ß-Carbomethoxy-3ß-(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.

Four-Minute Bone SPECT Using Large-Field Cadmium-Zinc-Telluride Camera.

PURPOSE: The 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. METHODS: Patients 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. RESULTS: Image 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. CONCLUSIONS: The 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.

The value of local normal limits in quantitative Thallium-201 CZT MPI SPECT.

BACKGROUND: Considering the distinctive characteristics of CZT detectors, automatic quantification of ischemia using normal limits included with software package may deliver suboptimal results for CAD detection. The present study aims to evaluate the benefits of creating normal limits specific to a local population and laboratory protocol. METHODS AND RESULTS: Two groups were selected from patients who had undergone a CZT MPI. Normal limits were generated with the QPS application based on the population with low likelihood of CAD. Using the vendor-supplied and the population-specific normal limits i-TPD and vessel-specific SDS results obtained for patients who had subsequently undergone coronary angiography were compared with coronary angiography data. A weak correlation was observed for low i-TPD (stress TPD minus rest TPD) and SDS values. Both databases gave similar values for the area under the ROC curve concerning i-TPD (0.75 to 0.74) and SDS results (0.72 to 0.75 for the LAD, 0.62 to 0.64 for the LCx, and 0.63 to 0.67 for the RCA). Sensitivity (60%), specificity (78%), and predictive positive (84%) and negative (52%) values were also similar with a diagnostic and prognostic threshold value. CONCLUSION: The use of a population-specific created database did not influence the diagnostic value of thallium-201 MPI QPS results using a CZT camera.

Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension.

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.

Discrete sequence production with and without a pause: the role of cortex, basal ganglia, and cerebellum.

Our sensorimotor experience unfolds in sequences over time. We hypothesize that the processing of movement sequences with and without a temporal pause will recruit distinct but cooperating neural processes, including cortico-striatal and cortico-cerebellar networks. We thus, compare neural activity during sequence learning in the presence and absence of this pause. Young volunteer participants learned sensorimotor sequences using the discrete sequence production (DSP) task, with Pause, No-Pause, and Control sequences of four elements in an event related fMRI protocol. The No-Pause and Pause sequences involved a more complex sequential structure than the Control sequence, while the Pause sequences involved insertion of a temporal pause, relative to the No-Pause sequence. The Pause vs. No-Pause contrast revealed extensive fronto-parietal, striatal, thalamic and cerebellar activations, preferentially for the Pause sequences. ROI analysis indicated that the cerebellum displays an early activation that was attenuated over successive runs, and a significant preference for Pause sequences when compared with caudate. These data support the hypothesis that a cortico-cerebellar circuit plays a specific role in the initial processing of temporal structure, while the basal ganglia play a more general role in acquiring the serial response order of the sequence.

Evaluation of a novel, noninvasive, objective test of auditory nerve function in cochlear implant candidates.

OBJECTIVE: To investigate whether the objective noninvasive recording of the electrically evoked amplitude modulation following response (EAMFR) can be applied for the assessment of auditory nerve function before cochlear implant surgery. STUDY DESIGN: Prospective clinical study from January 2005 to August 2008. SETTING: Cochlear Implant Program at the Charité University Hospital (Berlin, Germany). PATIENTS: One hundred twenty-one patients with severe to total bilateral sensorineural hearing impairment. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: All EAMFR thresholds were correlated with the mean intraoperative electrically evoked compound action potential (ECAP) thresholds. In a subgroup of 16 patients, the objective thresholds of the EAMFR were compared with the subjective auditory thresholds for the electrical stimuli applied. The intraindividual left-right concordance of the EAMFR and ECAP thresholds was investigated in 22 patients with bilateral implants. RESULTS: The EAMFR-auditory nerve function test produced clear responses in all patients examined. The threshold of auditory perception for the applied stimuli correlated highly significantly with the EAMFR threshold (r = 0.89, p < 0.01). The correlation between the EAMFR and mean ECAP thresholds was again highly significant (r = 0.49, p < 0.01). In all patients with bilateral implants, the ear with the lower preoperative EAMFR threshold was also the one with the lower intraoperative mean ECAP threshold. CONCLUSION: These results indicate that the objective noninvasive recording of EAMFR seems to be a useful diagnostic tool for the evaluation of the auditory nerve function in cochlear implant candidates, especially in children or in adult patients who require objective examination.

The neural bases of the constructive nature of autobiographical memories studied with a self-paced fMRI design.

In Conway and Pleydell-Pearce's model (2000), autobiographical memories are viewed as transitory mental representations, more often generated in an effortful way. An important claim of the model concerns the dynamic process that evolves over time, from the left prefrontal areas to posterior regions, to retrieve specific memories. The present work aims at investigating, using fMRI, the temporal distribution of effortful autobiographical memory construction. In addition, a self-paced design was implemented to elucidate the question of the timing window required to evoke recollections. The results showed a large pattern of brain regions, which included the two major poles of activation predicted by Conway and Pleydell-Pearce's model. Likewise, we were able to detect the earlier implication of the left dorso-lateral prefrontal cortex, by comparison with posterior structures, which seemed to confirm its involvement in the effortful retrieval process. Finally, the self-paced procedure allowed us to refine the timing window necessary to construct past events.

What neuroimaging tells us about sensory substitution.

A major question in the field of sensory substitution concerns the nature of the perception generated by sensory substitution prostheses. Is the perception determined by the nature of the substitutive modality or is it determined by the nature of the information transmitted by the device? Is it a totally new, amodal, perception? This paper reviews the recent neuroimaging studies which have investigated the neural bases of sensory substitution. The detailed analysis of available results led us to propose a general scheme of the neural mechanisms underlying sensory substitution. Two different main processes may be responsible for the visual area recruitment observed in the different studies: cross-modality and mental (visual) imagery. Based on our results analysis, we propose that cross-modality is the predominant process in early blind subjects whereas mental imagery is predominant in blindfolded sighted subjects. This model implies that, with training, sensory substitution mainly induces visual-like perception in sighted subjects and mainly auditory or tactile perception in blind subjects. This framework leads us to make some predictions that could easily be tested.

Material-independent cerebral network of re-experiencing personal events: evidence from two parallel fMRI experiments.

Two parallel fMRI experiments were conducted with the aim to clarify the lateralisation issue of the cerebral network underlying autobiographical memory retrieval independently of the stimulus material and the refreshment of the memory trace. The verbal experiment required a pre-scanning interview, while the nonverbal version tested the subjects directly during the fMRI session. Both experiments were constructed using the same experimental design to eliminate methodological variables in order to render comparisons possible. We found a predominantly left-lateralised cerebral network independently of material and regardless of whether or not memory traces were reactivated prior to the scanning session. We discuss the results in the context of neuroimaging studies of autobiographical memory (AbM).

Implicit emotion during recollection of past events: a nonverbal fMRI study.

Faces of other significant people are highly self-relevant and close to our everyday way of recollecting past events. We chose such stimuli to probe the emotional component of autobiographical memory retrieval. Photographs were collected from family members without the participant's involvement, thereby avoiding refreshment of the memory trace prior to the scanning session. We asked the subjects to spontaneously evoke a unique autobiographical episode following the presentation of relatives' and friends' faces. Famous faces recognition was used as a semantic memory control task. We carried out a post-fMRI debriefing session to collect participants' memories and their emotional intensity. The post-scanning behavioural data together with the neuroimaging data provided evidence that emotional aspects were implicitly involved during recollections. Our findings suggest that the use of highly self-relevant stimuli and the collection of data with no previous refreshment of the memory trace influence the right lateralisation of activations in the medial temporal lobe (MTL).

Neural changes in the ventral and dorsal visual streams during pattern recognition learning.

The learning process related to pattern and object recognition is difficult to study because the human brain has a remarkable capacity to recognise complex visual forms from early infancy. In the present study, we investigated on-going neural changes underlying the learning process of visual pattern recognition by means of a device substituting audition for vision. Functional MRI evidenced the gradual pattern recognition-induced recruitment of the ventral visual stream, bilaterally, from learning session 1 to session 3, and a slight decrease in these activation foci from session 3 to session 4. The initial increase in activation is thought to reflect the gradually enhanced visualisation of patterns in the subjects' mind across sessions. By contrast the subsequent decrease reported at the end of the training period is interpreted as the progressive optimisation of neuronal responses elicited by the task. Our results, in accordance with previous observations, suggest that the succession of activation increase and decrease in sensori-motor areas could be a general rule in sensory and sensori-motor learning.

Two cortical systems for reaching in central and peripheral vision.

Parietal lesions in humans can produce a specific disruption of visually guided hand movement, termed optic ataxia. The fact that the deficit mainly occurs in peripheral vision suggests that reaching in foveal and extrafoveal vision rely on two different neural substrates. In the present study, we have directly tested this hypothesis by event-related fMRI in healthy subjects. Brain activity was measured when participants reached toward central or peripheral visual targets. Our results confirm the existence of two systems, differently modulated by the two conditions. Reaching in central vision involved a restricted network including the medial intraparietal sulcus (mIPS) and the caudal part of the dorsal premotor cortex (PMd). Reaching in peripheral vision activated in addition the parieto-occipital junction (POJ) and a more rostral part of PMd. These results show that reaching to the peripheral visual field engages a more extensive cortical network than reaching to the central visual field.