Abnormal motor cortical plasticity as a useful neurophysiological biomarker for Alzheimer's disease pathology.

OBJECTIVE: Amyloid-beta (Aß) and tau accumulations impair long-term potentiation (LTP) induction in animal hippocampi. We investigated relationships between motor-cortical plasticity and biomarkers for Alzheimer's disease (AD) diagnosis in subjects with cognitive decline. METHODS: Twenty-six consecutive subjects who complained of memory problems participated in this study. We applied transcranial quadripuse stimulation with an interstimulus interval of 5 ms (QPS5) to induce LTP-like plasticity. Motor-evoked potentials were recorded from the right first-dorsal interosseous muscle before and after QPS5. Cognitive functions, Aß42 and tau levels in the cerebrospinal fluid (CSF) were measured. Amyloid positron-emission tomography (PET) with11C-Pittsburg compound-B was also conducted. We studied correlations of QPS5-induced plasticity with cognitive functions or AD-related biomarkers. RESULTS: QPS5-induced LTP-like plasticity positively correlated with cognitive scores. The degree of LTP-like plasticity negatively correlated with levels of CSF-tau, and the amount of amyloid-PET accumulation at the precuneus, and correlated with the CSF-Aß42 level positively. In the amyloid-PET positive subjects, non-responder rate of QPS5 was higher than the CSF-tau positive rate. CONCLUSIONS: Findings suggest that QPS5-induced LTP-like plasticity is a functional biomarker of AD. QPS5 could detect abnormality at earlier stages than CSF-tau in the amyloid-PET positive subjects. SIGNIFICANCE: Assessing motor-cortical plasticity could be a useful neurophysiological biomarker for AD pathology.

Construction of a Phantom for Image Quality Evaluation in PET/MRI System.

Background: There is no phantom for image quality test in magnetic resonance imaging combined with positron emission tomography systems (PET/MRI systems). In MRI, radioactive water phantom containing 2-deoxy-2-[F-18] fluoro-D-glucose (18F-FDG) cannot be used due to the dielectric effect. Even for phantoms filled with MR-available solutions, the source current of the RF coil is strongly disturbed as the diameter of the phantom increases. Stable MR images require proper phantom size and solution selection. Previous reports have not provided these details. Other than that, few existing phantoms evaluate negative signals such as N-13 ammonia (13N-NH3). We created a phantom for PET/MRI system for image quality test. Methods: The phantom for the PET/MRI system was assembled in two portions. One portion is a signal part containing 18F-FDG radioactive water. The other portion is filled with polyvinyl alcohol glue to construct MRI image to generate µ-map. The glue part is allowed to rewrite the table position overlaps with the first layer, and attenuation correction is performed. Signals are set as positive (4 times and twice higher than background radioactivity) and negative (no radioactivity) columns with different sizes (15 mm φ and 7 mm φ). The PET images with X-ray computed tomography-based attenuation correction (CT-AC) and MRI-AC were evaluated by %-contrasts, variation and uniformity. Results: The %-contrasts of the positive shallow signals with PET/magnetic resonance (MR) and PET/CT were 41.8% and 45.4%, respectively. And it of the positive deep signals with PET/MR and PET/CT were 40.7% and 44.9%. On the other hand, the %-contrasts of the negative shallow signals with PET/MR and PET/CT were 62.3% and 65.6%, respectively. And it of the negative deep signals with PET/MR and PET/CT were 60.7% and 63.7%. Moreover, the % Nj index of uniformity was 2.0% on PET/MRI images and 0.34% on PET/CT images. For negative signals that assume a decrease in myocardial blood flow, The image quality of MR-AC was almost the same as that of CT-AC. Consistency between the images after CT-AC and MR-AC correction were confirmed, and in particular, a stable MR-AC µ-map was obtained in the phantom study. Conclusion: The suggested prototype phantom for generating µ-map is reasonable and useful for evaluating PET/MRI image quality, based on the present standard.

A novel case of concurrent occurrence of demyelinating-polyneuropathy-causing PMP22 duplication and SOX10 gene mutation producing severe hypertrophic neuropathy.

BACKGROUND: Hereditary motor and sensory neuropathy, also referred to as Charcot-Marie-Tooth disease (CMT), is most often caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. This duplication causes CMT type 1A (CMT1A). CMT1A rarely occurs in combination with other hereditary neuromuscular disorders. However, such rare genetic coincidences produce a severe phenotype and have been reported in terms of "double trouble" overlapping syndrome. Waardenburg syndrome (WS) is the most common form of a hereditary syndromic deafness. It is primarily characterized by pigmentation anomalies and classified into four major phenotypes. A mutation in the SRY sex determining region Y-box 10 (SOX10) gene causes WS type 2 or 4 and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease. We describe a 11-year-old boy with extreme hypertrophic neuropathy because of a combination of CMT1A and WS type 2. This is the first published case on the co-occurrence of CMT1A and WS type 2. CASE PRESENTATION: The 11-year-old boy presented with motor developmental delay and a deterioration in unstable walking at 6 years of age. In addition, he had congenital hearing loss and heterochromia iridis. The neurological examination revealed weakness in the distal limbs with pes cavus. He was diagnosed with CMT1A by the fluorescence in situ hybridization method. His paternal pedigree had a history of CMT1A. However, no family member had congenital hearing loss. His clinical manifestation was apparently severe than those of his relatives with CMT1A. In addition, a whole-body magnetic resonance neurography revealed an extreme enlargement of his systemic cranial and spinal nerves. Subsequently, a genetic analysis revealed a heterozygous frameshift mutation c.876delT (p.F292Lfs*19) in the SOX10 gene. He was eventually diagnosed with WS type 2. CONCLUSIONS: We described a patient with a genetically confirmed overlapping diagnoses of CMT1A and WS type 2. The double trouble with the genes created a significant impact on the peripheral nerves system. Severe phenotype in the proband can be attributed to the cumulative effect of mutations in both PMP22 and SOX10 genes, responsible for demyelinating neuropathy.

Integrated PET/MRI scanner with oxygen-15 labeled gases for quantification of cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen.

OBJECTIVES: Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) by PET with oxygen-15 labeled gases is useful for diagnosis and treatment planning in cases of chronic occlusive cerebrovascular disease. In the present study, CBF, CBV, OEF and CMRO2 were measured using the integrated design of PET/MRI scanner system. This is a first attempt to measure cerebral perfusion and oxygen metabolism using PET/MRI with oxygen-15 labeled gases. METHODS: PET/MRI measurements with the steady-state method of oxygen-15 labeled gases, carbon monoxide (C15O), oxygen (15O2), and carbon dioxide (C15O2) were performed on nine healthy men. Two kinds of attenuation correction for PET were performed using MRI with Dixon sequence (DIXON) and Dixon sequence with model-based bone segmentation (DIXONbone). A real-time motion correction of PET images was also performed using simultaneously measured MR images to detect head motion. RESULTS: Mean and SD values of CBF, CBV, OEF, and CMRO2 in the cerebral cortices with attenuation correction by DIXON were 31 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.5 ± 0.3 mL/100 mL/min without real-time motion correction, and 33 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.6 ± 0.3 mL/100 mL/min with real-time motion correction, respectively. Values with of CBF, CBV, OEF, and CMRO2 with attenuation correction by DIXONbone were 35 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.8 ± 0.3 mL/100 mL/min without real-time motion correction, and 38 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 3.0 ± 0.4 mL/100 mL/min with real-time motion correction, respectively. CONCLUSIONS: Using PET/MRI with oxygen-15 labeled gases, CBF, CBV, OEF, and CMRO2 could be measured. Values of CBF, CBV, and CMRO2 measured with attenuation correction by DIXON were significantly lower than those measured with correction by DIXONbone. One of the reasons for this is that attenuation correction of DIXON does not take into consideration of the photon absorption by bone. OEF values, corresponding to ratios of CMRO2 to CBF, were not affected by attenuation correction methods. Values of CBF and CMRO2 with a real-time motion correction were significantly higher than those without correction. Using PET/MRI with adequate corrections, similar values of CBF, CBV, OEF, and CMRO2 as PET alone scanner system reported previously were obtained. TRAIL REGISTRATION: The UMIN clinical trial number: UMIN000033382.

Evaluation of a model-based attenuation correction method on whole-body 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging.

The bone cannot be evaluated using magnetic resonance attenuation correction (MRAC) with the Dixon sequence. To solve this issue, the present study aimed to evaluate model-based AC for whole-body 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) by creating bone segmentation. We analyzed and evaluated the data of 31 consecutive patients. The Biograph mMR (Siemens Healthcare) was used for clinical whole-body 18F-FDG PET/MRI with the conventional MRAC method, and OSIRIX MD software was used to analyze the images. After the examination, the new model-based post-processing MRAC was applied to create µ-maps with bone segmentation, and retrospective PET reconstruction was performed using this µ-map. The bone structures of all patients created using model-based MRAC were visually evaluated. Standard uptake values (SUVs) at 11 anatomical positions in PET images, corrected using the µ-map with and without bone segmentation, were measured and compared. The model-based post-processing MRAC was run for all patients, without errors. Visual evaluation revealed that the model-based post-processing MRAC exhibited poor results for six patients. Furthermore, it exhibited an increasing trend of SUV in the brain compared to the conventional method. Locations other than the brain indicated a similar or decreasing trend. The two methods showed a good linear correlation for all patients. However, patients aged < 20 years exhibited a different trend from those aged ≥ 20 years. We should exercise caution when applying this model-based MRAC for younger patients.

Time-related study on external exposure dose of 2-deoxy-2-[F-18]fluoro-D-glucose PET for workers' safety.

Time-course study of individual dose equivalents of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (18F-FDG PET) was conducted in different hospital workers, and the daily work duties were analyzed. For the measurements, a semiconductor dosimeter was used. The values at intervals of 1 min and 1 h, the monthly cumulative and daily cumulative doses, and trend graphs were acquired with dedicated software and displayed on the reader. The following radiation workers with duties involving maximum external exposure work were included: doctors making diagnoses (4.8 µSv/procedure), nurses removing injection needles (3.1 µSv/procedure), pharmacists performing quality control tests (2.9 µSv/procedure), nuclear medicine technologists assisting patient positioning (6.5 µSv/procedure), and cyclotron engineers performing daily checks (13.4 µSv/procedure). The results of analysis of daily work duties revealed the influencing factors of external exposure dose. To reduce the external exposure dose, investigators should shorten the patient's contact time with the 18F-FDG source or patient tracer.

Detectability of Malignant Lesions by Whole-Body Magnetic Resonance Imaging Using Whole-Body Integrated Positron Emission Tomography/Magnetic Resonance Imaging.

PURPOSE: To assess the diagnostic ability of whole-body magnetic resonance imaging (MRI) using integrated positron emission tomography/MRI(PET/MRI). METHODS: Axial T2-weighted image (T2WI), diffusion-weighted imaging (DWI), coronal T1-weighted image (T1WI), axial volumetric interpolated breath-hold examination in the lung field, and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG-PET) were evaluated in combination with T2WI alone, T2WI + DWI, T2WI + DWI + T1WI, T2WI + DWI + T1WI + volumetric interpolated breath-hold examination (all MRI images), and all MRI + FDG-PET. RESULTS: A total of 370 lesions were observed in 90 (62.5%) of the 144 patients. The lesion-based sensitivities were 62%, 74%, 74%, 76%, and 94%, and the patient-based sensitivities were 70%, 77%, 77%, 77%, and 81% using T2WI, T2WI + DWI, T2WI + DWI + T1WI, all MRI, and all MRI + FDG-PET, respectively. There were significant differences in the lesion-based sensitivity between T2WI and other sequence combinations and between all MRI and all MRI + FDG-PET. No significant differences were observed between any combinations among the patient-based sensitivities. CONCLUSION: The sensitivity of whole-body MRI was lower when lesion based, but almost equivalent when patient based compared with PET/MRI.

[Thoracoabdominal muscle involvement in anti-PL-7 myopathy revealed by whole-body magnetic resonance imaging].

A 33-year-old woman developed progressive weakness in the proximal limbs with myalgia and morning stiffness. Physical examination revealed low-grade fever, heliotrope eyelids and mechanic's hand. On neurological examination, she showed Medical Research Council grade 4 weakness in the shoulder girdle, proximal limb muscles, and grade 4 weakness in the abdominis muscle according to Daniels's scale. Laboratory tests revealed elevated serum creatine kinase (6,824 IU/l) and positive anti-PL-7 antibody. A needle electromyography study detected short motor unit potentials of myogenic pattern with abundant fibrillations and positive sharp waves. Whole-body MRI detected high intensity signals in the muscles of the shoulder girdle, proximal limbs, and thoracoabdominal trunk on short-tau inversion recovery sequence images. We diagnosed her as anti-PL-7 myopathy. After treatments with steroid, immunosuppressant, and immunoglobulin, her symptoms improved and abnormal MRI signals were normalized. Although MRI is known to be useful for detection of asymptomatic muscular inflammation in myositis, thoracoabdominal muscles are generally not covered in routine evaluation. To our knowledge, ours is the first case to detect acute inflammation of the thoracoabdominal muscles in antisynthetase syndrome. The present study suggests that whole-body MRI is useful for comprehensive evaluation of muscular involvement and longitudinal assessment for treatment outcomes.

Technical aspects of cardiac PET/MRI.

PET/MRI is a novel modality that enables to combine PET and MR images, and has significant potential to evaluate various cardiac diseases through the combination of PET molecular imaging and MRI functional imaging. Precise management of technical issues, however, is necessary for cardiac PET/MRI. This article describes several technical points, including patient preparation, MR attenuation correction, parallel acquisition of PET with MRI, clinical aspects, and image quality control.