Anatomical Variations of the Left Adrenal Vein Encountered During Venous Sampling.

PURPOSE: To identify anatomical variations in the left adrenal vein (LAV) and to evaluate the role of preprocedural contrast-enhanced computed tomography (CT) planning. METHODS: The length of the left adrenal central vein (LACV), the vessel that receives blood from all tributaries of the left adrenal gland, was measured using venograms of patients who had undergone adrenal venous sampling (AVS) for the diagnosis of primary aldosteronism between October 2017 and December 2019. The anatomical variants of the LAV were described and classified. Contrast-enhanced CT was used to evaluate the detection rate of the following: (a) confluence of the left inferior phrenic vein and the LAV and (b) the last tributary flowing into the LAV. RESULTS: In total, 311 patients (143 men, 168 women; mean age: 49.3 years ± 11.0) were enrolled. Of them, 9 (2.9%) patients had anatomical variants lacking a LACV. In patients with a LACV (n = 302), the venographic LACV length was 9.0 mm ± 3.9 (<1 mm in 9 patients). The detection rate of the confluence of the left inferior phrenic vein and LAV, as determined using contrast-enhanced CT, was high (96.2%), whereas that of the last tributary flowing into the LAV was low (0.8%). In 4 of 18 patients with short or absent LACV, the variant was visualized using contrast-enhanced CT. CONCLUSIONS: In some patients, the LACV is absent or short, which is an anatomical variation. Understanding venographic anatomical variations can help avoid misleading results resulting from a suboptimal sampling site in AVS. For some subtypes, contrast-enhanced CT may also help in planning the AVS procedure.

Pitfalls in chest CT findings of COVID-19 patients infected during hospitalisation.

OBJECTIVE: This study evaluated the differences in the appearance of COVID-19 pneumonia on chest computed tomography (CT) images of outpatient and cases that developed during hospitalisation. METHOD: Chest CT images of 66 patients (median age, 76 years; range, 29-94 years) who underwent the severe acute respiratory syndrome coronavirus-2 reverse-transcription polymerase chain reaction (RT-PCR) test were included in this retrospective study. The chest CT appearance was categorised as "typical," "indeterminate," "atypical," or "negative" in accordance with the recommendations of the Radiological Society of North America for COVID-19 pneumonia and compared among the following four subgroups: PCR-positive outpatient (n = 14); PCR-positive hospitalised (n = 7); PCR-negative outpatient (n = 9); and PCR-negative hospitalised (n = 36). FINDINGS: The frequency of "typical" findings in the PCR-positive outpatient cases (13/14, 92.9%) was significantly higher than that of those in the PCR-positive hospitalised cases (2/7, 28.6%, P = 0.022). There was no significant difference between the frequency of the "typical" appearance in PCR-positive hospitalised cases and that of those in the PCR-negative hospitalised cases (1/36, 2.8%, P = 0.192). CONCLUSIONS: When COVID-19 patients acquire infections while hospitalised, their chest CT images are less likely to show typical findings than those of outpatient cases. Comprehensive and careful assessments of CT findings and consideration of the possibility of concomitant infections with other pathogens and clinical information, such as underlying diseases, background lung structure, and time course of the infection, are required for the management of such cases.

Retention Mechanism of Proteins in Hydroxyapatite Chromatography - Multimodal Interaction Based Protein Separations: A Model Study.

BACKGROUND: Retention mechanism of proteins in hydroxyapatite chromatography (HAC) was investigated by linear gradient elution experiments (LGE). MATERIALS AND METHODS: Several mobile phase (buffer) solution strategies and solutes were evaluated in order to probe the relative contributions of two adsorption sites of hydroxyapatite (HA) particles, C-site due to Ca (metal affinity) and P-site due to PO4 (cation-exchange). When P-site was blocked, two basic proteins, lysozyme (Lys) and ribonuclease A(RNase), were not retained whereas cytochrome C(Cyt C) and lactoferrin (LF) were retained and also retention of acidic proteins became stronger as the repulsion due to P-site was eliminated. The number of the binding site B values determined from LGE also increased, which also showed reduction of repulsion forces. CONCLUSION: The selectivity (retention) of four basic proteins (RNase, Lys, Cyt C, LF) in HAC was different from that in ion-exchange chromatography. Moreover, it was possible to tune the selectivity by using NaCl gradient.

Salt tolerant chromatography provides salt tolerance and a better selectivity for protein monomer separations.

Salt tolerant chromatography (STC) is an attractive method as buffer exchange during protein purification processes can be skipped; however, the retention and separation mechanism of such STC are still not fully understood. We carried out linear gradient elution (LGE) experiments of bovine serum albumin (BSA) including its dimer form by using poly-amine ligand STC. The peak salt concentration IR was measured as a function of normalized gradient slope GH, and the number of binding sites B was determined. The separation performance of monomer and dimer was much higher for STC. The IR values of BSA monomer and dimer for STC were much higher (IR > 0.5M) than those for conventional IEC. The IR values of arginine-Cl gradient decreased markedly compared to those of NaCl gradient whereas they did not change for conventional IEC. This might be due to combined effects of electrostatic and hydrophobic interaction to the retention of proteins in STC. Adding polyethylene glycol (PEG) into the mobile phase of IEC also increased the retention (salt tolerance) and the resolution of BSA monomer and dimer. Higher viscosity and low solubility of proteins due to PEG were disadvantages of this method. STC with poly-amine ligand might be also suited for the continuous flow-through separation of monomer.

Microdevice for on-site fish freshness checking based on K-value measurement.

An electrochemical microfluidic device with two sensing sites in the upper and lower streams of a flow channel was fabricated to measure the K-value as a means of evaluating the freshness of fish. In this device, plugs of solutions were processed using mechanisms to place a plug at the sensing site and to merge and mix two plugs in a single flow channel. The sums of ATP-related compound concentrations used for the calculation of the K-value were measured at the first and second sensing sites. The ratio of the output currents agreed well with the K-value calculated from predetermined concentrations in standard solutions. The K-values of jack mackerel, yellow tail, and sea bream extracts were then obtained using the device and were found to agree well with those obtained by high-performance liquid chromatography (HPLC). In addition, the changes in the K-value with time were observed to depend strongly on the type of fish for these three fish extracts.

PEG chain length impacts yield of solid-phase protein PEGylation and efficiency of PEGylated protein separation by ion-exchange chromatography: insights of mechanistic models.

The mechanisms behind protein PEGylation are complex and dictated by the structure of the protein reactant. Hence, it is difficult to design a reaction process which can produce the desired PEGylated form at high yield. Likewise, efficient purification processes following protein PEGylation must be constructed on an ad hoc basis for each product. The retention and binding mechanisms driving electrostatic interaction-based chromatography (ion-exchange chromatography) of PEGylated proteins (randomly PEGylated lysozyme and mono-PEGylated bovine serum albumin) were investigated, based on our previously developed model Chem. Eng. Technol. 2005, 28, 1387-1393. PEGylation of each protein resulted in a shift to a smaller elution volume compared to the unmodified molecule, but did not affect the number of binding sites appreciably. The shift of the retention volume of PEGylated proteins correlated with the calculated thickness of PEG layer around the protein molecule. Random PEGylation was carried out on a column (solid-phase PEGylation) and the PEGylated proteins were separated on the same column. Solid-phase PEGylation inhibited the production of multi-PEGylated forms and resulted in a relatively low yield of selective mono-PEGylated form. Pore diffusion may play an important role in solid-phase PEGylation. These results suggest the possibility of a reaction and purification process development based on the mechanistic model for PEGylated proteins on ion exchange chromatography.

Integration of corticospinal tractography reduces motor complications after radiosurgery.

PURPOSE: To evaluate whether the use of diffusion-tensor tractography (DTT) of the corticospinal tract could reduce motor complications after stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Patients with arteriovenous malformation (AVM) in the deep frontal lobe, deep parietal lobe, basal ganglia, and thalamus who had undergone radiosurgery since 2000 and were followed up for more than 3 years were studied. DTT of the corticospinal tract had been integrated into treatment planning of SRS since 2004, and the maximum dose received by the corticospinal tract was attempted to be less than 20 Gy. Treatment outcomes before (28 patients, Group A) and after (24 patients, Group B) the introduction of this technique were compared. RESULTS: There were no statistical differences between the two groups (Group A vs. Group B) in patients' age (34 years vs. 33 years, p = 0.76), percentage of patients with hemorrhagic events before treatment (50% vs. 29%, p = 0.12), or percentage of AVM involving the basal ganglia and thalamus (36% vs. 46%, p = 0.46). Obliteration rates were 69% and 76% at 4 years in Groups A and B, respectively (p = 0.68), which were not significantly different. Motor complications were observed in 5 patients in Group A (17.9%) but only in 1 patient in Group B (4.2%), which was significantly less frequent (p = 0.021). CONCLUSION: Integrating DTT of the corticospinal tract into treatment planning contributed to reduction of motor complications without compromising the obliteration rate for AVM adjacent to the corticospinal tract.

Outcomes of diffusion tensor tractography-integrated stereotactic radiosurgery.

PURPOSE: To analyze the effect of use of tractography of the critical brain white matter fibers created from diffusion tensor magnetic resonance imaging on reduction of morbidity associated with radiosurgery. METHODS AND MATERIALS: Tractography of the pyramidal tract has been integrated since February 2004 if lesions are adjacent to it, the optic radiation since May 2006, and the arcuate fasciculus since October 2007. By visually confirming the precise location of these fibers, the dose to these fiber tracts was optimized. One hundred forty-four consecutive patients with cerebral arteriovenous malformations who underwent radiosurgery with this technique between February 2004 and December 2009 were analyzed. RESULTS: Tractography was prospectively integrated in 71 of 155 treatments for 144 patients. The pyramidal tract was visualized in 45, the optic radiation in 22, and the arcuate fasciculus in 13 (two tracts in 9). During the follow-up period of 3 to 72 months (median, 23 months) after the procedure, 1 patient showed permanent worsening of pre-existing dysesthesia, and another patient exhibited mild transient hemiparesis 12 months later but fully recovered after oral administration of corticosteroid agents. Two patients had transient speech disturbance before starting integration of the arcuate fasciculus tractography, but no patient thereafter. CONCLUSION: Integrating tractography helped prevent morbidity of radiosurgery in patients with brain arteriovenous malformations.

Dynamic spatiotemporal gene expression in embryonic mouse thalamus.

The anatomy of the mammalian thalamus is characterized by nuclei, which can be readily identified in postnatal animals. However, the molecular mechanisms that guide specification and differentiation of neurons in specific thalamic nuclei are still largely unknown, and few molecular markers are available for most of these thalamic subregions at early stages of development. We therefore searched for patterned gene expression restricted to specific mouse thalamic regions by in situ hybridization during the onset of thalamic neurogenesis (embryonic [E] days E10.5-E12.5). To obtain correct regional information, we used Shh as a landmark and compared spatial relationships with the zona limitans intrathalamica (Zli), the border of the p2 and p3 compartments of the diencephalon. We identified genes that are expressed specifically in the ventricular zone of the thalamic neuroepithelium and also identified a number of genes that already exhibited regional identity at E12.5. Although many genes expressed in the mantle regions of the thalamus at E12.5 showed regionally restricted patterns, none of these clearly corresponded to individual thalamic nuclei. We next examined gene expression at E15.5, when thalamocortical axons (TCAs) project from distinct regions of the thalamus and reach their targets in the cerebral cortex. Regionally restricted patterns of gene expression were again seen for many genes, but some regionally bounded expression patterns in the early postnatal thalamus had shifted substantially by E15.5. These findings reveal that nucleogenesis in the developing thalamus is associated with selective and complex changes in gene expression and provide a list of genes that may actively regulate the development of thalamic nuclei.

Region-specific gene expression in early postnatal mouse thalamus.

Previous studies in the developing mouse thalamus have demonstrated that regional identity is established during early stages of development (Suzuki-Hirano et al. J. Comp. Neurol. 2011;519:528-543). However, the developing thalamus often shows little resemblance to the anatomical organization of the postnatal thalamus, making it difficult to identify genes that might mediate the organization of thalamic nuclei. We therefore analyzed the expression pattern of genes that we have identified as showing regional expression in embryonic thalamus on postnatal days (P) 6-8 by using in situ hybridization. We also identified several genes expressed only in the postnatal thalamus with restricted expression in specific nuclei. We first demonstrated the selective expression of neurotransmitter-related genes (vGlut2, vGAT, D2R, and HTR2C), identifying the neurotransmitter subtypes of cells in this region, and we also demonstrated selective expression of additional genes in the thalamus (Steel, Slitrk6, and AI852580). In addition, we demonstrated expression of genes specific to somatosensory thalamic nuclei, the ventrobasal posterior nuclei (VP); a visual thalamic nucleus, the dorsal lateral geniculate nucleus (dLGN); and an auditory thalamic nucleus, the medial geniculate body (MGB) (p57Kip, Nr1d1, and GFRα1). We also identified genes that are selectively expressed in multiple different nuclei (Foxp2, Chst2, and EphA8). Finally, we demonstrated that several bone morphogenetic proteins (BMPs) and their inhibitors are expressed in the postnatal thalamus in a nucleus-specific fashion, suggesting that BMPs play roles in the postnatal thalamus unrelated to their known role in developmental patterning. Our findings provide important information for understanding the mechanisms of nuclear specification and connectivity during development, as well as their maintenance in adult thalamus.

High signal intensity in the dural sinuses on 3D-TOF MR angiography at 3.0 T.

PURPOSE: The objective of this study was to examine the frequency of high signal intensity in the dural sinuses of normal subjects upon magnetic resonance (MR) angiography using 3.0-T scanners. METHODS: A total of 748 consecutive healthy subjects underwent three-dimensional time-of-flight MR angiography at 3.0 T. Sixteen subjects were excluded. MR angiographic source images were retrospectively reviewed for the presence of high signal intensity in the inferior petrosal sinus, pterygoid sinus, or sigmoid sinus. RESULTS: Of the 732 examinations, 10 (1.3%) showed high signal intensity in the dural sinuses (left inferior petrosal sinus, n=4; left pterygoid sinus, n=3; left sigmoid sinus, n=6). High signal intensity in the dural sinuses was observed only on the left side. The minimum diameter of the left brachiocephalic vein was significantly smaller in subjects with high signal intensity than in the control group. CONCLUSION: In our study with healthy subjects at 3.0 T, the frequency of high signal intensity in the dural sinuses is as low as 1.3%. Retrograde flow due to physiological stenosis of the left brachiocephalic vein may be one of the causes of this phenomenon.

Contrast-enhanced magnetic resonance characteristics of arteriovenous malformations after γ knife radiosurgery: predictors of post-angiographic obliteration hemorrhage.

BACKGROUND: The reported cumulative risk of post-angiographic obliteration (post-AO) hemorrhage from arteriovenous malformations (AVMs) following gamma knife radiosurgery (GKRS) over 10 years is 2.2%. OBJECTIVE: To identify the warning signs of post-AO hemorrhage by analyzing the characteristics of enhancement on contrast-enhanced MRI magnetic resonance imaging (MRI) of AVMs with post-AO hemorrhage. METHODS: We performed a retrospective analysis of 121 patients whose AVMs were angiographically obliterated within 5 years of GKRS without hemorrhage and who received at least 1 contrast-enhanced MRI after GKRS (group 1), and 7 patients who experienced post-AO hemorrhage (group 2). We analyzed the enhancement persistence ratio (the percentage of AVMs with persisting enhancement on contrast-enhanced T1-weighted image after obliteration) and the change in size of the enhanced region over time in each patient. RESULTS: The enhancement persistence ratio showed no significant difference between the 2 groups (89.4% vs 100% for groups 1 and 2, respectively; P=.401). While most cases in group 1 showed a tendency to decrease in size and gradually stabilize following GKRS, there were significantly more cases in group 2 with obvious increment of the enhanced regions within 1 year of angiographic obliteration compared with the previous measurement (4.96% vs 71.4% for groups 1 and 2, respectively; P<.0001). CONCLUSION: Our results suggest that AVMs that show an increase in the size of the enhanced region within 1 year of angiographic obliteration should be followed up with caution for post-AO hemorrhage. Persisting enhancement itself is not positively associated with subsequent hemorrhage.

Arcuate fasciculus tractography integrated into Gamma Knife surgery.

OBJECT: To prevent speech disturbances after Gamma Knife surgery (GKS), the authors integrated arcuate fasciculus (AF) tractography based on diffusion tensor (DT) MR imaging into treatment planning for GKS. METHODS: Arcuate fasciculus tractography was retrospectively integrated into planning that had been previously performed by neurosurgeons and radiation oncologists. This technique was retrospectively applied to 12 patients with arteriovenous malformations adjacent to the AF. Diffusion tensor images were acquired before the frame was affixed to the patient's head and DT tractography images of the AF were created using the authors' original software. The data from DT tractography and stereotactic 3D imaging studies obtained after frame fixation were transported to a treatment planning workstation for GKS and coregistered so that the delivered doses and incidence of posttreatment aphasia could be assessed. RESULTS: The AF could not be depicted in 2 patients who initially presented with motor aphasia caused by hemorrhaging from arteriovenous malformations. During the median follow-up period of 29 months after GKS, aphasia developed in 2 patients: 30 Gy delivered to the frontal portion of the AF caused conduction aphasia in 1 patient, and 9.6 Gy to the temporal portion led to motor aphasia in the other. Speech dysfunction was not observed after a maximum radiation dose of 10.0-16.8 Gy was delivered to the frontal fibers in 4 patients, and 3.6-5.2 Gy to the temporal fibers in 3. CONCLUSIONS: The authors found that administration of a 10-Gy radiation dose during GKS was tolerated in the frontal but not the temporal fibers of the AF. The authors recommend confirmation of the dose by integration of AF tractography with GKS, especially in lesions located near the temporal language fibers.

Assessment of arteriovenous malformations with 3-Tesla time-resolved, contrast-enhanced, three-dimensional magnetic resonance angiography.

OBJECT: Although conventional catheter angiography is commonly used in the evaluation of intracranial arteriovenous malformations (AVMs), less invasive tools are more suitable for screening or follow-up. Older MR angiography techniques cannot provide high enough temporal and spatial resolution for assessing AVMs. Threetesla time-resolved imaging of contrast kinetics (TRICKS)-a time-resolved, contrast-enhanced 3D MR angiography technique-achieves subsecond time resolution without sacrificing spatial resolution. The purpose of this study was to assess the accuracy of TRICKS at 3 T in the evaluation of AVMs. METHODS: Between November 2006 and November 2007, 31 patients who were known to have AVMs underwent evaluation in a 3-T unit with the TRICKS technique. The TRICKS images were then evaluated independently by 2 radiologists for nidus detection, early venous filling detection, and Spetzler-Martin classification, and these results were compared with the results of catheter angiography. RESULTS: Time-resolved imaging of contrast kinetics achieved 96% sensitivity and 100% specificity both in nidus detection and early venous filling detection. The Spetzler-Martin grades also showed excellent correlation with catheter angiography findings (kappa= 0.89). CONCLUSIONS: Although this is a preliminary study, the authors' results indicate that time-resolved contrast-enhanced 3D MR angiography at 3 T is a good tool to assess AVMs, and has the potential to replace catheter angiography in screening or follow-up examinations of patients with AVMs.

Tolerance of pyramidal tract to gamma knife radiosurgery based on diffusion-tensor tractography.

PURPOSE: To minimize the morbidity of radiosurgery for critically located lesions, we integrated diffusion-tensor tractography into treatment planning for gamma-knife radiosurgery. We calculated the refined tolerance of the pyramidal tract (PT) after prospective application of the technique to additional patients. METHODS AND MATERIALS: The relationship between the dosimetry during treatment planning and the development of subsequent motor complications was investigated in 24 patients, 9 studied retrospectively and 15 studied prospectively. The maximal dose to the PT and the volumes of the PT that received > or = 20 Gy (20-Gy volume) and > or = 25 Gy (25-Gy volume) were calculated. Univariate logistic regression analyses were used to produce dose-response curves. Differences in the tolerable dose according to the PT location were calculated. RESULTS: Univariate logistic regression analysis of the motor complications revealed a significant independent correlation with the maximal dose to the PT and the 20- and 25-Gy volumes. The maximal dose to the PT with a 5% risk of motor complications was 23 Gy compared with 15 Gy in our previous report. The risk of motor complications was significantly greater in the internal capsule than in the corona radiata for the 20- and 25-Gy volumes in generalized Wilcoxon tests (p = 0.031), although no significant difference was observed for the maximal dose. CONCLUSION: The tolerable dose of the PT was greater than that previously reported. The internal capsule was more sensitive to high-dose irradiation over a wide area of the PT, probably owing to the dense concentration of motor fibers.

Optic radiation tractography integrated into simulated treatment planning for Gamma Knife surgery.

OBJECT: No definitive method of preventing visual field deficits after stereotactic radiosurgery for lesions near the optic radiation (OR) has been available so far. The authors report the results of integrating OR tractography based on diffusion tensor (DT) magnetic resonance imaging into simulated treatment planning for Gamma Knife surgery (GKS). METHODS: Data from imaging studies performed in 10 patients who underwent GKS for treatment of arteriovenous malformations (AVMs) located adjacent to the OR were used for the simulated treatment planning. Diffusion tensor images performed without the patient's head being secured by a stereotactic frame were used for DT tractography, and the OR was visualized by means of software developed by the authors. Data from stereotactic 3D imaging studies performed after frame fixation were coregistered with the data from DT tractography. The combined images were transferred to a GKS treatment-planning workstation. Delivered doses and distances between the treated lesions and the OR were analyzed and correlated with posttreatment neurological changes. RESULTS: In patients presenting with migraine with visual aura or occipital lobe epilepsy, the OR was located within 11 mm from AVMs. In a patient who developed new quadrantanopia after GKS, the OR had received 32 Gy. A maximum dose to the OR of less than 12 Gy did not cause new visual field deficits. A maximum dose to the OR of 8 Gy or more was significantly related to neurological change (p < 0.05), including visual field deficits and development or improvement of migraine. CONCLUSIONS: Integration of OR tractography into GKS represents a promising tool for preventing GKS-induced visual disturbances and headaches. Single-session irradiation at a dose of 8 Gy or more was associated with neurological change.

Utilization of diffusion tensor tractography in combination with spatial normalization to assess involvement of the corticospinal tract in capsular/pericapsular stroke: Feasibility and clinical implications.

PURPOSE: To investigate the feasibility of using spatial normalization in combination with diffusion tensor (DT) corticospinal tractography to assess corticospinal tract (CST) involvement in capsular or pericapsular stroke. MATERIALS AND METHODS: Corticospinal tractograms were created and segmented out using DT imaging (DTI) data from 10 normal volunteers. After spatial normalization was achieved with statistical parametric mapping (SPM), the whole ensemble of tractograms was used as a map of the CST. This was overlaid on the infarction site, which had also been spatially normalized from isotropic diffusion-weighted (DW) images of 14 patients with small symptomatic capsular or pericapsular infarction. We evaluated the extent of CST involvement within the infarction site. Differences were sought in relation to recovery of muscle strength. RESULTS: The CST was engulfed by the infarction in all patients. Muscle strength recovery occurred in 10 of the 14 patients. The extent of cross-sectional and longitudinal involvement in the infarction site was related to motor recovery (P = 0.041). CONCLUSION: An evaluation of the involvement of the CST in cases of capsular or pericapsular infarction utilizing DT fiber tractography in combination with spatial normalization was found to be feasible as it clearly visualized the extent of CST involvement consistent with the symptom.

Evaluation of left ventricular function with cardiac magnetic resonance imaging using Fourier fitting.

The aims of this study were to investigate the applicability of Fourier fitting in the magnetic resonance (MR) evaluation of left ventricular (LV) function and to determine the optimal number of harmonics for fitting. Cine cardiac MR imaging was performed in 10 subjects, and an LV time-volume curve was generated. Fourier fitting was applied to the original curve using 1-10 harmonics, and the qualities of the time-volume curve and first-derivative curve were evaluated. LV functional parameters were calculated from curves generated with and without fitting. The quality of the original time-volume curve was good, and Fourier fitting had no substantial effect on functional parameters obtained directly from the time-volume curve such as ejection fraction. The first-derivative curve generated without fitting showed substantial artificial fluctuation. The application of Fourier fitting depressed the fluctuation and tended to decrease estimates of peak ejection rate and peak filling rate. Five or six harmonics appeared to be appropriate for obtaining a high-quality first-derivative curve. In conclusion, Fourier fitting was indicated to aid in reducing the artificial fluctuation of the first-derivative curve generated from cine cardiac MR imaging and to contribute to the evaluation of functional parameters derived from the first-derivative curve.