Background: The habenula is involved in the pathophysiology of depression. However, its small structure limits the accuracy of segmentation methods, and the findings regarding its volume have been inconsistent. This study aimed to create a highly accurate habenula segmentation model using deep learning, test its generalizability to clinical magnetic resonance imaging, and examine differences between healthy participants and patients with depression. Methods: This multicenter study included 382 participants (patients with depression: N = 234, women 47.0%; healthy participants: N = 148, women 37.8%). A 3-dimensional residual U-Net was used to create a habenula segmentation model on 3T magnetic resonance images. The reproducibility and generalizability of the predictive model were tested on various validation cohorts. Thereafter, differences between the habenula volume of healthy participants and that of patients with depression were examined. Results: A Dice coefficient of 86.6% was achieved in the derivation cohort. The test-retest dataset showed a mean absolute percentage error of 6.66, indicating sufficiently high reproducibility. A Dice coefficient of >80% was achieved for datasets with different imaging conditions, such as magnetic field strengths, spatial resolutions, and imaging sequences, by adjusting the threshold. A significant negative correlation with age was observed in the general population, and this correlation was more pronounced in patients with depression (p < 10-7, r = -0.59). Habenula volume decreased with depression severity in women even when the effects of age and scanner were excluded (p = .019, η2 = 0.099). Conclusions: Habenula volume could be a pathophysiologically relevant factor and diagnostic and therapeutic marker for depression, particularly in women.
Accurate segmentation of the habenula, a brain region implicated in depression, is challenging. In this study, we developed an automated human habenula segmentation model using deep learning techniques. The model was confirmed to be reproducible and generalizable at various spatial resolutions. Application of this model to a multicenter dataset confirmed that habenula volume decreased with age in healthy volunteers, an association that was more pronounced in individuals with depression. In addition, habenula volume decreased with the severity of depression in women. This novel model for habenula segmentation enables further study of the role of the habenula in depression.
BACKGROUND: Sensitive detection and quantification of cerebral glucose is desired. PURPOSE: To quantify cerebral glucose by detecting the H1-α-glucose peak at 5.23 ppm in 1 H magnetic resonance spectroscopy at 7 T. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight non-fasted healthy subjects (aged 20-28 years). FIELD STRENGTH/SEQUENCE: Short echo time stimulated echo acquisition mode (short-TE STEAM) and semi-localized by adiabatic selective refocusing (semi-LASER) at 7 T. ASSESSMENT: Single voxel spectra were obtained from the posterior cingulate cortex (27-mL) using a 32-channel head coil. The H1-α-glucose peak in the spectrum with retrospective removal of the residual water peak was fitted using LCModel with a glucose basis set of only the H1-α-glucose peak. Conventional spectral analysis was performed with a glucose basis set of a full spectral pattern of glucose, also. Fitting precision was evaluated with Cramér-Rao lower bounds (CRLBs). The repeatability of glucose quantification via the semi-LASER sequence was tested. STATISTICAL TESTS: Paired or Welch's t-test were used for normally distributed values. A P value of <0.05 was considered significant. The repeatability of measures was analyzed using coefficient of variation (CV). RESULTS: Removal of the residual water peak improved the flatness and stability of baselines around the H1-α-glucose peak and reduced CRLBs for fitting the H1-α-glucose peak. The semi-LASER sequence was superior to the short-TE STEAM in the higher signal-to-noise ratio of the H1-α-glucose peak (mean ± SD 7.9 ± 2.5, P < 0.001). The conventional analysis overfitted the H1-α-glucose peak. The individual CVs of glucose quantification by detecting the H1-α-glucose peak were smaller than the corresponding CRLBs. DATA CONCLUSION: Cerebral glucose concentration is quantitated to be 1.07 mM by detecting the H1-α-glucose peak in the semi-LASER spectra. Despite requiring long scan times, detecting the H1-α-glucose peak allows true glucose quantification free from the influence of overlapping taurine and macromolecule signals. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.
Brain , Water , Humans , Prospective Studies , Retrospective Studies , Magnetic Resonance Spectroscopy/methods , Signal-To-Noise Ratio , Brain/diagnostic imaging , Brain/metabolism
The present study investigated the differences between digital [18F]-Fluorodeoxyglucose (FDG) positron emission tomography [PET]/computed tomography [CT] (dPET/CT) and conventional PET/CT (cPET/CT) in delineating the clinical target volume (CTV) in patients with advanced lung cancer in the involved field radiation therapy (IFRT) era. Patients with advanced lung cancer were scanned using two dual-imaging protocols (dPET/CT and cPET/CT). Two virtual delineations contoured with reference to dPET/CT and cPET/CT images were created for each patient by five radiation oncologists. Changes in the delineation of target volumes in each patient were examined. A total of 10 patients [male/female, 9/1; median age, 65 years (range, 58-80 years)] were enrolled between April 2020 and September 2020. Significant changes in the delineation of CTVs were uncommon between dPET/CT and cPET/CT. A notable increase in CTVn was observed in 10% of the patients (1/10; P<0.05; Smirnov-Grubbs analysis). In this patient, a node that was not assessed as lymph node metastasis when cPET/CT was used was assessed as lymph node metastasis when dPET/CT was used and was included in the CTVn by all five radiation oncologists. In patients with advanced lung cancer, notable changes in CTV delineations are uncommon, regardless of whether dPET/CT or cPET/CT is used. However, in some cases, CTVn delineation with reference to dPET/CT may improve the treatment outcomes of IFRT for advanced lung cancer.
Recent high-performance gradient coils are fabricated mainly at the expense of spatial linearity. In this study, we measured the spatial nonlinearity of the magnetic field generated by the gradient coils of two MRI systems with high-performance gradient coils. The nonlinearity of the gradient fields was measured using 3D gradient echo sequences and a spherical phantom with a built-in lattice structure. The spatial variation of the gradient field was approximated to the 3rd order polynomials. The coefficients of the polynomials were calculated using the steepest descent method. The geometric distortion of the acquired 3D MR images was corrected using the polynomials and compared with the 3D images corrected using the harmonic functions provided by the MRI venders. As a result, it was found that the nonlinearity correction formulae provided by the vendors were insufficient and needed to be verified or corrected using a geometric phantom such as used in this study.
The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.
Brain Diseases , Leukoaraiosis , White Matter , Middle Aged , Humans , White Matter/diagnostic imaging , Aging , Magnetic Resonance Imaging/methods , Cerebral Cortex/diagnostic imaging , Gray Matter/diagnostic imaging
Rationale and objectives: Macromolecules (MMs) affect the precision and accuracy of neurochemical quantification in magnetic resonance spectroscopy. A measured MM basis is increasingly used in LCModel analysis combined with a spline baseline, whose stiffness is controlled by a parameter named DKNTMN. The effects of measured MM basis and DKNTMN were investigated. Materials and methods: Twenty-six healthy subjects were prospectively enrolled and scanned twice using a short echo-time Stimulated Echo Acquisition Mode (STEAM) at 7-T. Using LCModel, analyses were conducted using the simulated MM basis (MMsim) with DKNTMN 0.15 and an MM basis measured inhouse (MMmeas) with DKNTMN of 0.15, 0.30, 0.60 and 1.00. Cramér-Rao lower bound (CRLB) and the concentrations of gamma-aminobutyric acid (GABA), glutamate and excitatory-inhibitory ratio (EIR), in addition to MMs were statistically analyzed. Measurement stability was evaluated using coefficient of variation (CV). Results: CRLBs of GABA were significantly lower when using MMsim than MMmeas; those of glutamate were 2-3. GABA concentrations were significantly higher in the analysis using MMsim than MMmeas where concentrations were significantly higher with DKNTMN of 0.15 or 0.30 than 0.60 or 1.00. Difference in glutamate concentration was not significant. EIRs showed the same difference as in GABA depending on the DKNTMN values. CVs between test-retest scans were relatively stable for glutamate but became larger as DKNTMN increased for GABA and EIR. Conclusion: Neurochemical quantification depends on the parameters of the basis sets used for fitting. Analysis using MMmeas with DKNTMN of 0.30 conformed best to previous studies and is recommended.
Carbonyl stress is a condition featuring increased rich reactive carbonyl compounds, which facilitate the formation of advanced glycation end products including pentosidine. We previously reported the relationship between enhanced carbonyl stress and disrupted white matter integrity in schizophrenia, although which microstructural component is disrupted remained unclear. In this study, 32 patients with schizophrenia (SCZ) and 45 age- and gender-matched healthy volunteers (HC) were recruited. We obtained blood samples for carbonyl stress markers (plasma pentosidine and serum pyridoxal) and multi-modal magnetic resonance imaging measures of white matter microstructures including apparent axonal density (intra-cellular volume fraction (ICVF)) and orientation (orientation dispersion index (ODI)), and inflammation (free water (FW)). In SCZ, the plasma pentosidine level was significantly increased. Group comparison revealed that mean white matter values were decreased for ICVF, and increased for FW. We found a significant negative correlation between the plasma pentosidine level and mean ICVF values in SCZ, and a significant negative correlation between the serum pyridoxal level and mean ODI value in HC, regardless of age. Our results suggest an association between enhanced carbonyl stress and axonal abnormality in SCZ.
Schizophrenia , White Matter , Humans , Schizophrenia/diagnostic imaging , White Matter/diagnostic imaging , Pyridoxal , Glycation End Products, Advanced , Axons
Frontotemporal dementia and/or amyotrophic lateral sclerosis 6, also known as amyotrophic lateral sclerosis 14, is an autosomal dominant, progressive neurodegenerative disorder caused by various mutations in the valosin-containing protein gene. In this report, we examined a 51-year-old female Japanese patient with frontotemporal dementia and amyotrophic lateral sclerosis. The patient began noticing gait disturbances at the age of 45 years. Neurological examination at the age of 46 years met the Awaji criteria for clinically probable amyotrophic lateral sclerosis. At the age of 49 years, she tended to have poor mood and an aversion to activity. Her symptoms gradually worsened. She required a wheelchair for transport and had difficulty communicating with others because of poor comprehension. She then began to frequently exhibit irritability. Eventually, she was admitted to the psychiatric hospital because uncontrollable violent behavior throughout the day. Longitudinal brain magnetic resonance imaging revealed progressive brain atrophy with temporal dominance, non-progressive cerebellar atrophy, and some non-specific white matter intensities. Brain single photon emission computed tomography showed hypoperfusion in the bilateral temporal lobes and cerebellar hemispheres. Clinical exome sequencing revealed the presence of a heterozygous nonsynonymous variant (NM_007126.5, c.265C>T; p.Arg89Trp) in the valosin-containing protein gene, which was absent in the 1000 Genomes Project, the Exome Aggregation Consortium Database, and the Genome Aggregation Database, and was predicted to be "damaging" by PolyPhen-2 and "deleterious" using SIFT with a Combined Annotation Dependent Depletion score of 35. We also confirmed the absence of this variant in 505 Japanese control subjects. Therefore, we concluded that the variant in the valosin-containing protein gene was responsible for the symptoms of this patient.
PURPOSE: Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT. MATERIALS AND METHODS: From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134 mmol/L) and hyperkalemia (serum potassium level ≥ 5.0 mmol/L). RESULTS: Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019). CONCLUSION: THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.
Hyperkalemia , Hyponatremia , Thyroid Neoplasms , Thyrotropin Alfa , Humans , Thyrotropin Alfa/therapeutic use , Iodine Radioisotopes/adverse effects , Hyperkalemia/chemically induced , Hyperkalemia/drug therapy , Hyponatremia/chemically induced , Hyponatremia/drug therapy , Retrospective Studies , Thyrotropin/therapeutic use , Potassium/therapeutic use , Sodium/therapeutic use , Electrolytes/therapeutic use
We aimed to clarify whether dopamine depletion in the posterior dorsal striatum in early-stage Parkinson's disease (PD) alters synchronized activity in the cortico-basal ganglia motor circuit. In sum, 14 PD patients and 16 matched healthy controls (HC) underwent [11C]-2-ß-carbomethoxy-3-ß-(4-fluorophenyl) tropane positron emission tomography to identify striatal dopamine-depleted areas. The identified map was applied to functional magnetic resonance imaging (fMRI) to discover abnormalities in functional connectivity (FC) during motor-task and rest-state in PD patients in the drug-off state relative to HC. Striatal dopamine-depleted areas formed synchronized fMRI activity that largely corresponded to the cortico-basal ganglia motor circuit. Group comparisons revealed that striatal dopamine-depleted areas exhibited decreased FC with the medial premotor cortex during motor-task and with the medial, lateral premotor and primary motor cortices during rest-state. Striatal dopamine-depleted areas also elucidated decreased FC in the subthalamic nucleus (STN) in PD both during motor-task and rest-state. The STN regions that exhibited reduced FC with striatal dopamine-depleted areas demonstrated excessive FC with the lateral premotor and primary motor cortices in PD only during rest-state. Our findings suggest that striatal dopamine-depleted area reduced synchronized activity with the motor cortices and STN, which, in turn, induces an abnormal increase in coupling between the areas in PD.
BACKGROUND: Diagnostic guidelines for isolated cardiac sarcoidosis (iCS) were first proposed in 2016, but there are few reports on the imaging and prognosis of iCS. This study aimed to evaluate the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in predicting iCS prognosis. METHODS AND RESULTS: We retrospectively reviewed the clinical and imaging data of 306 consecutive patients with suspected CS who underwent FDG PET/CT with a dedicated preparation protocol and included 82 patients (55 with systemic sarcoidosis including cardiac involvement [sCS], 27 with iCS) in the study. We compared the FDG PET/CT findings between the two groups. We examined the relationship between the CS type and the rate of adverse cardiac events. The iCS group had a significantly lower target-to-background ratio than the sCS group (P = 0.0010). The event-free survival rate was significantly lower in the iCS group than the sCS group (log-rank test, P < 0.0001). iCS was identified as an independent prognostic factor for adverse events (hazard ratio 3.82, P = 0.0059). CONCLUSION: iCS was an independent prognostic factor for adverse cardiac events in patients with CS. The clinical diagnosis of iCS based on FDG PET/CT and new guidelines may be important.
Cardiomyopathies , Myocarditis , Sarcoidosis , Humans , Positron Emission Tomography Computed Tomography , Fluorodeoxyglucose F18 , Retrospective Studies , Radiopharmaceuticals , Prognosis , Positron-Emission Tomography/methods
The morphologies of the fetal tentorium cerebelli (TC) and brain influence each other during development. This study aimed to analyze and more comprehensively understand the three-dimensional morphogenesis of the TC and fetal brain. We examined magnetic resonance imaging from 64 embryonic and fetal specimens (crown-rump length range, 9.2-225 mm). During the embryonic period, the lateral folds of the TC elongated to traverse the middle part of the midbrain. The TC and falx cerebri appeared separated, and no invaginations at the parieto-occipital region were observed. In the early fetal period, the cerebrum covered approximately half of the midbrain. The separation of the dural limiting layer at the parieto-occipital region widened from the posterior cerebrum to the cranial cerebellum. The lateral folds of the TC were spread between its tip, continuous with the falx cerebri, and its base plane, located between the midbrain and rostral hindbrain. Differences in the TC components' growth directions gradually diminished as the cerebrum covered the midbrain. We observed rotation of the TC at its median section according to its growth, which ceased in the middle fetal period. The brainstem and cerebellum extended inferiorly via differential growth, with the cerebrum covering them superiorly. The morphology of the TC curved to conform to the cerebellar and cerebral surfaces. Our present study suggests that factors affecting TC morphology differ between the early and middle fetal periods. Present data provided a more comprehensive view of TC formation according to developmental stage.
Brain , Dura Mater , Humans , Dura Mater/anatomy & histology , Brain/diagnostic imaging , Cerebellum/diagnostic imaging , Skull , Fetal Development
Background: Solitary fibrous tumor/hemangiopericytomas (SFT/HPCs) are rare mesenchymal tumors of nonmeningothelial origin that comprises <1% of all central nervous system tumors. Case Description: A 45-year-old male presented with sleep apnea (apnea-hypopnea index was 17.1 events/hour) and dysesthesias of the right upper and lower extremities. The magnetic resonance demonstrated a heterogeneous intradural extra-axial C1 mass with syringobulbia and syringomyelia. The right vertebral angiography revealed a hypervascular mass (i.e., intense tumor staining). With the preoperative diagnosis of a spinal hemangioblastoma, the patient underwent tumor removal. However, intraoperative findings demonstrated that the ventral component of the tumor was intramedullary without a dural attachment. Further, the histological diagnosis was consistent with SFT/HPC (HPC phenotype). The postoperative course was uneventful, and the patient's symptoms and the syrinxes spontaneously regressed. Conclusion: A 45-year-old male presented a rare spinal intradural lesion at C1 appeared to be a spinal hemangioblastoma, but proved to be SFT/HPC (HPC phenotype) with intramedullary invasion.
Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders.
OBJECTIVE: The motor severity in Parkinson disease (PD) is believed to parallel dopaminergic terminal degeneration in the striatum, although the terminal was reported to be virtually absent by 4 years postdiagnosis. Meanwhile, neuromelanin-laden dopamine neuron loss in the substantia nigra (SN) elucidated a variability at early stages and gradual loss with less variability 10 years postdiagnosis. Here, we aimed to clarify the correlation between motor impairments and striatal dopaminergic terminal degeneration and nigral neuromelanin-laden dopamine neuron loss at early to advanced stages of PD. METHODS: Ninety-three PD patients were divided into early and advanced subgroups based on motor symptom duration and whether motor fluctuation was present. Striatal dopaminergic terminal degeneration was evaluated using a presynaptic dopamine transporter tracer, 123 I-ioflupane single photon emission computed tomography (SPECT). Nigral neuromelanin-laden dopamine neuron density was assessed by neuromelanin-sensitive magnetic resonance imaging (NM-MRI). RESULTS: In patients with early stage PD (motor symptoms for ≤8 or 10 years), motor dysfunction during the drug-off state was paralleled by a decline in 123 I-ioflupane uptake in the striatum despite the absence of a correlation with reductions in NM-MRI signals in SN. Meanwhile, in patients with advanced stage PD (motor symptoms for >8 or 10 years and with fluctuation), the degree of motor deficits during the drug-off state was not correlated with 123 I-ioflupane uptake in the striatum, despite its significant negative correlation with NM-MRI signals in SN. INTERPRETATION: We propose striatal dopaminergic terminal loss measured using 123 I-ioflupane SPECT and nigral dopamine neuron loss assessed with NM-MRI as early stage and advanced stage motor impairment biomarkers, respectively. ANN NEUROL 2022;92:110-121.
Parkinson Disease , Corpus Striatum/metabolism , Dopamine , Dopamine Plasma Membrane Transport Proteins/metabolism , Dopaminergic Neurons/pathology , Humans , Magnetic Resonance Imaging/methods , Nerve Degeneration/diagnostic imaging , Nerve Degeneration/pathology , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Substantia Nigra/pathology , Tomography, Emission-Computed, Single-Photon/methods
Background: Anterior inferior cerebellar artery (AICA) aneurysms in the internal auditory canal (IAC) are rare. We have reported a case of dissecting AICA aneurysm in the IAC presenting initially with the eighth nerve palsy followed by the seventh nerve palsy without hemorrhage. Case Description: A 68-year-old woman presented with a sudden onset of vertigo accompanied by deafness and tinnitus on the right side that was preceded by intermittent right retroauricular pain 2 weeks before. Audiogram showed severe sensorineural hearing loss. Computed tomography and magnetic resonance imaging (MRI) indicated absence of prior subarachnoid hemorrhage. Magnetic resonance angiogram (MRA) suggested a tiny aneurysm at the fundus of the IAC accompanied with thinning of the lateral pontine segment of the AICA. Conservative treatment led to moderate improvement of the symptoms. However, the patient developed the right retroauricular pain again, followed by the right facial paralysis 5 months later but still without signs of hemorrhage on MRI. Digital subtraction angiogram showed dissecting aneurysm in the IAC. The patient was managed with oral steroids and direct intervention was avoided due to a risk of ischemia supposed by large area irrigated by the AICA. Follow-up MRA 18 months after the first presentation showed improvement in the narrowing of the AICA proximal to the aneurysm. The patient was functionally independent despite right-sided hearing loss and slight facial paresis. Conclusion: This report warns physicians that a dissecting AICA aneurysm without subarachnoid hemorrhage may cause eighth and seventh nerve palsy.
