Embolic stroke induced by rotational persistent 1st intersegmental artery compression.

A 45-year-old man suffered multiple cerebral infarctions in the vertebrobasilar artery territory, followed by second stroke against conservative treatment. Radiological examinations revealed intra-arterial defect in left persistent 1st intersegmental artery (PFIA) at C1 level, suggesting mural thrombus, and mechanical compression of left PFIA at the level with head rotation to the right clearly revealed by reconstructed 3-dimensional radiological images, but no findings of atlantoaxial instability. One month after the second stroke, posterior fixation was performed. Postoperative course was uneventful without subsequent stroke for 24 months. This unique case demonstrated that PFIA might associate with cerebral stroke as a clinical condition of bow hunter's stroke even in middle age. Reconstructed 3-dimensional radiological images might be useful for clear demonstration of the pathophysiology in this complex clinical entity.

Two-Dimensional Wavenumber Analysis Implemented in Ultrasonic Vector Doppler Method with Focused Transmit Beams.

The multi-angle Doppler method was introduced for the estimation of velocity vectors by measuring axial velocities from multiple directions. We have recently reported that the autocorrelation-based velocity vector estimation could be ameliorated significantly by estimating the wavenumbers in two dimensions. Since two-dimensional wavenumber estimation requires a snapshot of an ultrasonic field, the method was first implemented in plane wave imaging. Although plane wave imaging is predominantly useful for examining blood flows at an extremely high temporal resolution, it was reported that the contrast in a B-mode image obtained with a few plane wave emissions was lower than that obtained with focused beams. In this study, the two-dimensional wavenumber analysis was first implemented in a framework with focused transmit beams. The simulations showed that the proposed method achieved an accuracy in velocity estimation comparable to that of the method with plane wave imaging. Furthermore, the performances of the methods implemented in focused beam and plane wave imaging were compared by measuring human common carotid arteries in vivo. Image contrasts were analyzed in normal and clutter-filtered B-mode images. The method with focused beam imaging achieved a better contrast in normal B-mode imaging, and similar velocity magnitudes and angles were obtained by both the methods with focused beam and plane wave imaging. In contrast, the method with plane wave imaging gave a better contrast in a clutter-filtered B-mode image and smaller variances in velocity magnitudes than those with focused beams.

Bilateral carotid artery dissection due to Eagle syndrome in a patient with vascular Ehlers-Danlos syndrome: a case report.

BACKGROUND: Patients with vascular Ehlers-Danlos syndrome (EDS) occasionally suffer from arterial dissection. Eagle syndrome, which is caused by an elongated styloid process and also causes arterial dissection, is difficult to diagnose and could sometimes be overlooked. Little is known of the coexistence of these two diseases, and treatment strategy is not established. Here, we present a case of bilateral internal carotid artery (ICA) dissection due to Eagle syndrome in a patient with vascular EDS. CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of sudden onset of mild sensory disturbance in his left limbs. He had a history of Ehlers-Danlos syndrome (EDS) and also had left cervical internal carotid artery (ICA) dissection 3 years before. Diffusion-weighted imaging showed acute cerebral infarcts in the right hemisphere. Cervical computed tomography angiography (CTA) revealed the right ICA narrowing at the cervical portion in addition to the previous left cervical ICA dissection. Cervical magnetic resonance imaging (MRI) revealed double-lumen and intramural hematoma at the narrowing portion of the right cervical ICA, which indicates arterial dissection. CT also revealed bilateral elongated styloid processes which are close to each side of cervical ICA. We diagnosed him as bilateral ICA dissection due to bilateral Eagle syndrome. Considering vascular complications due to vascular EDS, we performed closer follow-up with transoral carotid ultrasonography (TOCU). In 4 months, his right ICA dissection gradually improved without stroke recurrence or deterioration of dissection. CONCLUSIONS: Since patients with vascular EDS easily develop arterial dissection, Eagle syndrome may be overlooked. Clinicians should consider Eagle syndrome in the case of vascular EDS with extracranial ICA dissection and close follow-up should be prioritized in cases of Eagle syndrome with vascular EDS.

Lectin Bead Array in a Single Tip Facilitates Fully Automatic Glycoprotein Profiling.

A quantitative description of glyco-alteration/differences in diseases can lead to the development of a diagnostic agent for use in vitro to monitor the degree of change in target glycoproteins. Analytical systems have been developed along with the progress of omics-oriented technologies. For clinical implementation, their full automation is required with an apparatus that is simple to operate. Here, we report an automatic analysis system for quantitative characterization of glyco-alteration/differences that depends on the unique strategy of "bead arrays in a single tip." The alternative lectin array can obtain a minimum characterization of the glycan profile for nanogram quantities of an endogenous glycoprotein. A simple autopipetting robot produces the precise chemiluminescence detection of glycan-lectin interactions with a wide dynamic range that is superior to fluorescence-based lectin arrays. The tip-based array format enables automatic glycan profiling from sample pretreatment to detection with low variation and linear detection, which may facilitate the use of this lectin array in clinical practice.

Flip-Flop Phenomenon: Swallowing-Induced Arterial Displacement as an Indicator of Carotid Artery Disease.

BACKGROUND AND PURPOSE: The dynamic displacement of the carotid arteries with interference of the hyoid bone during swallowing, named as "flip-flop" phenomenon (FFP), may be associated with ischemic stroke. However, the extent to which FFP is prevalent in carotid artery disease remains unknown. We aimed to investigate its exact prevalence to explore the relationship between FFP and carotid artery disease. METHODS: We examined 202 consecutive patients who were affected by neurological diseases including cerebrovascular diseases. Using carotid ultrasound, we evaluated carotid intima-media thickness, internal carotid artery stenosis (ICS), and FFP during swallowing with neck rotation. RESULTS: FFP was observed in 39 of the 202 patients (19.3%). Patients with FFP showed significantly higher prevalence of ICS than those without FFP (12/39 [30.8] vs. 21/163 [12.9%]; p = 0.007). Among those with ICS (n = 33; 36 vessels), FFP was associated with symptomatic ICS more frequently than with asymptomatic ICS (6/11 [54.5] vs. 5/25 [20.0%]; p = 0.038). Among those with unilateral FFP (n = 37), the prevalence of ipsilateral ICS was higher than that of contralateral ICS (9/37 [24.3] vs. 2/37 [5.4%]; p = 0.035). CONCLUSIONS: FFP accompanies the swallowing movement in some neurological patients, and more frequently in patients with ICS. FFP may thus be a novel indicator of stroke.

PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors.

The molecular mechanisms underlying the development of pancreatic neuroendocrine tumors (PanNETs) have not been well defined. We report here that the genomic region of the PHLDA3 gene undergoes loss of heterozygosity (LOH) at a remarkably high frequency in human PanNETs, and this genetic change is correlated with disease progression and poor prognosis. We also show that the PHLDA3 locus undergoes methylation in addition to LOH, suggesting that a two-hit inactivation of the PHLDA3 gene is required for PanNET development. We demonstrate that PHLDA3 represses Akt activity and Akt-regulated biological processes in pancreatic endocrine tissues, and that PHLDA3-deficient mice develop islet hyperplasia. In addition, we show that the tumor-suppressing pathway mediated by MEN1, a well-known tumor suppressor of PanNETs, is dependent on the pathway mediated by PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET development. Collectively, these results indicate the existence of a novel PHLDA3-mediated pathway of tumor suppression that is important in the development of PanNETs.

Evaluation of micro-emboli in a patient with ventricular assist device support with hemolysis.

The clinical relevance of transcranial Doppler (TCD) detection of micro-embolic signals (MES) in patients with ventricular assist devices (VADs) has been described. However, all of the previous studies concerning TCD in patients with VADs were conducted in patients with old devices; the clinical relevance of TCD in patients with newer devices has not been fully elucidated. We recently encountered a patient with a continuous-flow VAD with hemolysis. TCD monitoring was useful for the direct evaluation of micro-emboli in this patient. A 50-year-old male who underwent HeartMate II(®) VAD (Thoratec Corporation; Pleasanton, CA) implantation with a diagnosis of ischemic cardiomyopathy 15 months prior was admitted to our institution because of findings suggestive of hemolysis, such as elevated lactate dehydrogenase (LDH) and total bilirubin. Unfractionated heparin was started after admission and hemolysis gradually improved. On admission, TCD detected 146 MES during 30 min of monitoring. During the hospital course, the MES count decreased to 20 signals on hospital day 4 and further decreased to 2 signals on hospital day 15 along with decreases in LDH and total bilirubin. Since hemolysis in VAD patients is thought to be associated with thromboembolic outcomes, MES detected by TCD indicate subclinical micro-emboli. TCD monitoring may be useful for assessing the risk of thromboembolic events in newer continuous-flow VAD patients through direct visualization of micro-emboli.

Contrast-enhanced ultrasound for the evaluation of neovascularization in atherosclerotic carotid artery plaques.

BACKGROUND AND PURPOSE: Neovascularization associated with plaque vulnerability, particularly in the plaque shoulder, is susceptible to rupture, causing ischemic events. We aimed to use contrast-enhanced ultrasound to evaluate neovessels in carotid plaques quantitatively, focusing on plaque shoulders. METHODS: Using contrast-enhanced ultrasound with perflubutane, we analyzed 50 consecutive patients who underwent carotid endarterectomy. We measured enhanced intensity and assessed the correlation between contrast effect and histopathology, comparing symptomatic and asymptomatic plaques. RESULTS: Enhanced intensity of the plaque shoulder was associated with neovessel density (P<0.01; ρ=0.43). Enhanced intensity of the plaque shoulder was higher in plaques with rupture than in those without (P<0.05), and in symptomatic plaques (n=31) than in asymptomatic ones (n=19; P<0.01). CONCLUSIONS: Quantitative evaluation of the contrast effect using contrast-enhanced ultrasound enabled the assessment of neovascularization of plaque shoulders in vivo real time, which may help stratify plaque vulnerability.

Validation of ultrasound parameters to assess collateral flow via ophthalmic artery in internal carotid artery occlusion.

This study aimed to characterize the flow patterns using ultrasound (US) in the external carotid artery (ECA) in patients with total occlusion of internal carotid artery (ICA) and characterize collateral retrograde flow through the ophthalmic artery (OA, secondary collateral, internalization). This study was performed on 45 patients who were retrospectively selected with total occlusion of the ICA, who underwent digital subtraction angiography (DSA), magnetic resonance angiography (MRA), and US (43 men; mean age 68.1 ± 7.9 years). Collateral retrograde flow and collateral flow through the circle of Willis (primary collateral) were determined by DSA and MRA. We compared several US parameters such as ECA peak systolic velocity, mean velocity, end-diastolic (ED) velocity, pulsatility index (PI), and pulsatility transmission index (PTI). PTI was defined as the ratio of ipsilateral ECA PI to the ipsilateral common carotid artery (CCA). In this patient group, 27 patients showed retrograde flow through OA as assessed by DSA. The presence of primary collateral flow was significantly lower in patients with retrograde flow than without (P < .05). ECA ED velocity was significantly higher, and PI and PTI were significantly lower with retrograde flow through OA than without (P < .05). According to receiver operating characteristic analysis, PTI was the most highly correlated ultrasonologic parameter with internalization (cutoff value, .94; sensitivity, 92.6%; specificity, 94.5%). Using PTI was discriminative to determine internalization of ECA because a collateral pathway through OA in cases of ICA occlusion had less primary collateral pathways.

Usefulness of "AcT ratio" in diagnosis of internal carotid artery stenosis: a multicenter, retrospective, observational study.

PURPOSE: The ratio of the internal carotid artery (ICA) to the common carotid artery (CCA), especially the "AcT ratio," which is a modified measurement method of acceleration time, is useful for diagnosing ICA-origin stenosis. However, previous studies were single-center studies. Therefore, this multicenter, retrospective, cross-sectional study aimed to determine whether a method using the AcT ratio is useful for estimating stenosis rates. METHODS: This study included 461 vessels subjected to carotid artery ultrasonography and evaluation for ICA-origin stenosis via NASCET at four hospitals. The duration from the steep rise point to the inflection point or the first peak was defined as AcT on pulsed wave Doppler. The AcT ratio was calculated as AcT of ICA/AcT of ipsilateral CCA. The AcT ratio and rate of ICA-origin stenosis were analyzed using Pearson's correlation coefficient, simple regression analysis, and ROC curve. RESULTS: A significant positive correlation was observed between the AcT ratio and NASCET stenosis. NASCET stenosis of ≥ 50% had a sensitivity, specificity, and negative predictive value (NPV) of 70.2%, 71.6%, and 91.5%, respectively, when the cut-off value of the AcT ratio was 1.17. NASCET stenosis of ≥ 70% had a sensitivity, specificity, and NPV of 70.5%, 72.1%, and 95.9%, respectively, when the cut-off value of the AcT ratio was 1.22. CONCLUSIONS: The findings of this multicenter, retrospective, cross-sectional study suggest that the AcT ratio is useful for diagnosing ICA-origin stenosis, especially for diagnosis by exclusion. NASCET stenosis of ≥ 50% was considered unlikely if the Act ratio was ≤ 1.17, whereas NASCET stenosis of ≥ 70% was considered unlikely if it was ≤ 1.22.

Transcranial contrast-enhanced ultrasonography with Sonazoid in semiquantitative evaluation of brain perfusion.

PURPOSE: To semiquantitatively evaluate brain perfusion by transcranial contrast-enhanced ultrasonography (TCEUS) using Sonazoid. METHODS: We performed TCEUS in 11 healthy volunteers and seven patients with occlusive cerebrovascular disease involving the anterior circulation. After recording first-pass perfusion images on one side of the head and flush-replenishment (FR) images on both sides, we measured the time from arrival to peak (TAP) and peak intensity (PI) at first pass. Using the FR method, plateau value (A) and rise rate (ß) of intensity (I) were obtained from the curve I(t) = A(1 - e (-ß*t) ). RESULTS: In the patients, TAP was longer and PI was smaller in middle cerebral artery (MCA) areas than in posterior cerebral artery (PCA) areas on the ipsilesional side of the head (p < 0.05). A and ß were smaller in MCA areas than in PCA areas on the ipsilesional side of the head (p < 0.05), while these parameters showed no apparent differences between MCA and PCA areas in the volunteers. CONCLUSION: TCEUS with Sonazoid allows effective semiquantitative evaluation of brain perfusion.

An Ultrasonographic Evaluation for the Early Detection of Nerve Root Changes in Herpes Zoster-associated Motor Paresis.

We herein report a case of herpes zoster complicated by right-arm paralysis, wherein cervical nerve root ultrasonography enabled the early diagnosis and a therapeutic efficacy evaluation. A 71-year-old man developed progressive weakness in the muscles innervated by the right C5-6 nerve root following the appearance of a painful rash. Cervical nerve root ultrasonography revealed C5-6 nerve root inflammatory swelling. Methylprednisolone pulse therapy and subsequent oral prednisolone therapy gradually improved the muscle weakness. At three weeks following admission, ultrasonography revealed C5-6 nerve root inflammatory swelling improvement. Ultrasonography may aid in the early detection of nerve root inflammatory swelling and help monitor treatment efficacy.

Development of evaluation system for cerebral artery occlusion in emergency medical services: noninvasive measurement and utilization of pulse waves.

Rapid reperfusion therapy can reduce disability and death in patients with large vessel occlusion strokes (LVOS). It is crucial for emergency medical services to identify LVOS and transport patients directly to a comprehensive stroke center. Our ultimate goal is to develop a non-invasive, accurate, portable, inexpensive, and legally employable in vivo screening system for cerebral artery occlusion. As a first step towards this goal, we propose a method for detecting carotid artery occlusion using pulse wave measurements at the left and right carotid arteries, feature extraction from the pulse waves, and occlusion inference using these features. To meet all of these requirements, we use a piezoelectric sensor. We hypothesize that the difference in the left and right pulse waves caused by reflection is informative, as LVOS is typically caused by unilateral artery occlusion. Therefore, we extracted three features that only represented the physical effects of occlusion based on the difference. For inference, we considered that the logistic regression, a machine learning technique with no complex feature conversion, is a reasonable method for clarifying the contribution of each feature. We tested our hypothesis and conducted an experiment to evaluate the effectiveness and performance of the proposed method. The method achieved a diagnostic accuracy of 0.65, which is higher than the chance level of 0.43. The results indicate that the proposed method has potential for identifying carotid artery occlusions.

Neovascularization From the Carotid Artery Lumen Into the Carotid Plaque Confirmed by Contrast-Enhanced Ultrasound and Histology.

OBJECTIVE: This study was aimed at assessing intraplaque neovessels, focusing on neovascularization from the vascular luminal side using contrast-enhanced ultrasound (CEUS) and determining that this contrast effect indicates that the neovessel is connected to the vessel lumen histopathologically. Whether plaque vulnerability can be assessed more accurately was also investigated. METHODS: We enrolled consecutive patients with internal carotid artery stenosis who underwent carotid endarterectomy (CEA) and pre-operative CEUS with perflubutane of the carotid arteries. We graded the contrast effect semi-quantitatively from the vascular luminal and adventitial sides. We compared the contrast effect with the pathological findings, especially the neovascularization of the CEA specimens. RESULTS: In total, 68 carotid arterial atheromatous plaques (47 symptomatic) were analyzed. Symptomatic plaques were significantly correlated with stronger contrast effects from the luminal side than from the adventitial side (p = 0.0095). Microbubbles from the luminal side appeared to flow mainly into the plaque shoulder. The contrast effect value for the plaque shoulder and neovessel density were significantly correlated (ρ = 0.35, p = 0.031). Neovessel density was significantly higher in symptomatic than in asymptomatic plaques (56.2 ± 43.7/mm2 and 18.1 ± 15.2/mm2, respectively, p < 0.0001). Serial histological sections of CEA specimens in a symptomatic plaque with a strong contrast effect from the luminal side revealed multiple neovessels fenestrated to the vessel lumen with endothelial cells, consistent with the CEUS findings. CONCLUSION: Contrast-enhanced ultrasound can be used to evaluate neovessels originating from the luminal side, histopathologically confirmed in serial sections. Symptomatic vulnerable plaque is correlated more significantly with intraplaque neovascularization from the luminal side than with neovascularization from the adventitia.

Ultrasound-guided computed tomography angiography for the diagnosis of rotational vertebral artery occlusion: 2 case reports and technical notes.

Rotational vertebral artery occlusion is a rare cause of ischemic stroke in the vertebrobasilar arteries. While computed tomography angiography (CTA) is less invasive for the diagnosis of rational vertebral artery occlusion than digital subtraction angiography and more useful for elucidating the correlation between vertebrobasilar arteries and the surrounding structure, carotid ultrasound is noninvasive and more beneficial for the real-time evaluation of the hemodynamic change with neck rotation compared to CTA. Here, we reported 2 cases of rotational vertebral artery occlusion in patients aged 81 and 38 years and proposed a novel technique for its diagnosis using ultrasound-guided CTA. We suggest that the combination of ultrasound and CTA is useful for diagnosing rotational vertebral artery occlusion, which would compensate for the disadvantages of CTA alone.

Age and composition of the thrombus retrieved by mechanical thrombectomy from patients with acute ischemic stroke are associated with revascularization and clinical outcomes.

INTRODUCTION: Understanding the composition of stroke thrombi retrieved by mechanical thrombectomy is essential to clarify the pathogenesis of stroke. However, it is difficult to evaluate thrombus composition precisely and objectively. Immunohistochemical staining was used to evaluate thrombus composition and age. MATERIALS AND METHODS: Consecutive thrombi (n = 108) retrieved from patients who underwent mechanical thrombectomy for acute large-vessel ischemic stroke were retrospectively analyzed. Lytic features of granulocytes and CD163 were estimated as indicators of the age of the cardioembolic (CE) thrombus. RESULTS: The stroke subtypes were as follows: CE, 74 cases; large artery atherosclerosis, 11; undetermined etiology, 12; and other determined etiology, 11. There were no statistical differences in thrombi composition according to stroke subtypes. The fibrin area was positively correlated with the red blood cell (RBC) and platelet areas. The following analysis was performed using CE only. Regarding age, the thrombus was judged as fresh in 30.0 % and older in 70.0 % based on the lytic features. The RBC areas of older thrombi were smaller than those of fresh thrombi. The puncture-to-reperfusion time of older thrombi was longer than that of fresh thrombi. Platelet-rich thrombi were associated with a greater number of maneuvers, a smaller prevalence of TICI 3, and unfavorable functional outcomes compared to platelet-poor thrombi. The number of CD163 positive cells in thrombi with anticoagulants was higher than in those without anticoagulants. CONCLUSION: Thrombus composition correlated with revascularization and clinical outcomes. The composition of an acute ischemic thrombus may reflect the pathophysiology of stroke and influence treatment efficacy.

Investigation of feasibility of singular value decomposition clutter filter in plane wave imaging with packet transmission sequence.

PURPOSE: Assessment of blood flow is an important function in diagnostic ultrasound imaging. Color flow imaging is one such method widely used in the clinical setting. Since autocorrelation suffers from aliasing, the time interval between successive transmissions of ultrasonic pulses should be as short as possible. For this purpose, a specific transmit-receive sequence, namely, packet transmission, is widely used in color flow imaging. Also, plane wave imaging recently introduced to ultrasound imaging significantly contributes to improvement of the temporal resolution. Furthermore, a singular value decomposition (SVD) clutter filter reportedly outperforms a conventional clutter filter. In the present study, the feasibility of the SVD clutter filter in plane wave imaging with the packet transmission sequence was investigated. METHOD: In the present study, the packet transmission sequence was implemented in plane wave imaging by sending plane waves multiple times in the same direction before changing the steering angle. In the first strategy, like conventional color flow imaging with line-by-line acquisition using a focused transmit beam, a clutter filter was applied to ultrasonic radio-frequency (RF) signals in each packet. In the second strategy, the number of transmissions per packet was set at two, and a clutter filter was applied to RF signals obtained from the first or second transmission in different packets. RESULTS: The in vivo experimental results on a human carotid artery showed that the second strategy with an SVD filter realized significantly better performance than the first strategy with a polynomial regression filter used as a conventional filter. CONCLUSION: An SVD clutter filter was feasible in plane wave imaging with the packet transmission sequence, and the performance was improved by limiting the number of transmissions per packet to two.

Measurement of flow velocity vectors in carotid artery using plane wave imaging with repeated transmit sequence.

PURPOSE: Doppler-based methods are widely used for blood flow imaging in clinical settings. However, they inherently estimate the velocity component only in the axial direction. Therefore, various studies of angle-independent methods have been conducted. The multi-angle Doppler method is one such angle-independent method, in which the velocity vector is estimated using axial velocities obtained from multiple directions by steering an ultrasonic beam. Recently, plane wave imaging, which realizes a very high frame rate of several thousand frames per second, was applied to the multi-angle Doppler method. However, the maximum detectable velocity, i.e., the aliasing limit, was reduced depending on the number of steering angles. In the present study, the feasibility of a specific transmit sequence, namely, the repeated transmit sequence, was examined using the plane-wave multi-angle Doppler method. METHOD: In the repeated transmit sequence, plane waves were emitted to the same direction twice, after which the steering angle was changed. By repeating the same procedure, a pair of beamformed radio-frequency (RF) signals could be obtained under each beam steering angle. By applying the autocorrelation method to each pair of RF signals, the time interval between the RF signals could be kept as the pulse repetition interval (PRI). The feasibility of such a transmit sequence was examined by numerical simulation and in vivo measurement of a human carotid artery. RESULTS: The simulation results showed that the maximum steering angles of over 10 degrees were not feasible with the linear array used in the present study. The feasible maximum steering angle would depend on the element pitch of the probe relative to the ultrasonic wavelength. By limiting the maximum steering angles to 5 and 10 degrees, bias errors were 9.2% and 11.3%, respectively, and root mean squared errors were 21.5% and 16.9%, respectively. Also, flow velocity vectors in a human carotid artery could be visualized with the proposed method. CONCLUSION: The multi-angle Doppler method was implemented in plane wave imaging with the repeated transmit sequence, and the proposed method was shown to be feasible through numerical simulation and in vivo measurement of a carotid artery.

Simulation study on the effects of cancellous bone structure in the skull on ultrasonic wave propagation.

The transcranial Doppler method (TCD) enables the measurement of cerebral blood flow velocity and detection of emboli by applying an ultrasound probe to the temporal bone window, or the orbital or greater occipital foramina. TCD is widely used for evaluation of cerebral vasospasm after subarachnoid hemorrhage, early detection of patients with arterial stenosis, and the assessment of brain death. However, measurements often become difficult in older women. Among various factors contributing to this problem, we focused on the effect of the diploe in the skull bone on the penetration of ultrasound into the brain. In particular, the effect of the cancellous bone structure in the diploe was investigated. Using a 2D digital bone model, wave propagation through the skull bone was investigated using the finite-difference time-domain (FDTD) method. We fabricated digital bone models with similar structure but different BV/TV (bone volume/total volume) values in the diploe. At a BV/TV of approximately 50-60% (similar to that of older women), the minimum ultrasound amplitude was observed as a result of scattering and multiple reflections in the cancellous diploe. These results suggest that structural changes such as osteoporosis may be one factor hampering TCD measurements.