Comprehensive Die Shear Test of Silicon Packages Bonded by Thermocompression of Al Layers with Thin Sn Capping or Insertions.

Thermocompression bonding for wafer-level hermetic packaging was demonstrated at the lowest temperature of 370 to 390 °C ever reported using Al films with thin Sn capping or insertions as bonding layer. For shrinking the chip size of MEMS (micro electro mechanical systems), a smaller size of wafer-level packaging and MEMS⁻ASIC (application specific integrated circuit) integration are of great importance. Metal-based bonding under the temperature of CMOS (complementary metal-oxide-semiconductor) backend process is a key technology, and Al is one of the best candidates for bonding metal in terms of CMOS compatibility. In this study, after the thermocompression bonding of two substrates, the shear fracture strength of dies was measured by a bonding tester, and the shear-fractured surfaces were observed by SEM (scanning electron microscope), EDX (energy dispersive X-ray spectrometry), and a surface profiler to clarify where the shear fracture took place. We confirmed two kinds of fracture mode. One mode is Si bulk fracture mode, where the die shear strength is 41.6 to 209 MPa, proportionally depending on the area of Si fracture. The other mode is bonding interface fracture mode, where the die shear strength is 32.8 to 97.4 MPa. Regardless of the fracture modes, the minimum die shear strength is practical for wafer-level MEMS packaging.

Comparison of fluorescence optical imaging, ultrasonography and clinical examination with magnetic resonance imaging as a reference in active rheumatoid arthritis patients.

BACKGROUND: Fluorescence optical imaging with indocyanine-green enhancement (FOI) is a new imaging modality for the assessment of hand arthritis. The objective of this study was to compare performance profiles of clinical examination (CE), US and FOI using MRI as a reference in the same active rheumatoid arthritis (RA) patients. METHODS: CE, US, FOI and MRI were performed on six subjects with active RA. Each sequence of FOI was divided into three phases based on indocyanine-green dynamics and the joints were graded semi-quantitatively. Sensitivities and specificities of CE, US and FOI were calculated using the RAMRIS synovitis score >0 as a reference in a total of 30 joints (the second to fifth metacarpophalangeal (MCP) joints and the wrist of the clinically dominant hand). RESULTS: FOI showed sensitivities and specificities, respectively, of 85% and of 94% for Phase-1 and 69% and 94% for Phase-2. Sensitivities and specificities were 100% and 35% for CE (tender or swollen), 92% and 41% for gray scale US, and 77% and 100% for color-Doppler US. CONCLUSIONS: The performance characteristics of FOI in detection of synovitis in patients with active RA are comparable to those of US and more specific than CE. FOI has a potential as an assessment modality of RA.

Advanced LSI-based amperometric sensor array with light-shielding structure for effective removal of photocurrent and mode selectable function for individual operation of 400 electrodes.

We have developed a large-scale integrated (LSI) complementary metal-oxide semiconductor (CMOS)-based amperometric sensor array system called "Bio-LSI" as a platform for electrochemical bio-imaging and multi-point biosensing with 400 measurement points. In this study, we newly developed a Bio-LSI chip with a light-shield structure and a mode-selectable function with the aim of extending the application range of Bio-LSI. The light shield created by the top metal layer of the LSI chip significantly reduces the noise generated by the photocurrent, whose value is less than 1% of the previous Bio-LSI without the light shield. The mode-selectable function enables the individual operation of 400 electrodes in off, electrometer, V1, and V2 mode. The off-mode cuts the electrode from the electric circuit. The electrometer-mode reads out the electrode potential. The V1-mode and the V2-mode set the selected sensor electrode at two different independent voltages and read out the current. We demonstrated the usefulness of the mode-selectable function. First, we displayed a dot picture based on the redox reactions of 2.0 mM ferrocenemethanol at 400 electrodes by applying two different independent voltages using the V1 and V2 modes. Second, we carried out a simultaneous detection of O2 and H2O2 using the V1 and V2 modes. Third, we used the off and V1 modes for the modification of the osmium-polyvinylpyridine gel polymer containing horseradish peroxidase (Os-HRP) at the selected electrodes, which act as sensors for H2O2. These results confirm that the advanced version of Bio-LSI is a promising tool that can be applied to a wide range of analytical fields.

Diffusion-weighted magnetic resonance imaging in management of bladder cancer, particularly with multimodal bladder-sparing strategy.

Bladder-sparing strategy for muscle-invasive bladder cancer (MIBC) is increasingly demanded instead of radical cystectomy plus urinary diversion. Multimodal therapeutic approaches consisting of transurethral resection, chemotherapy, radiotherapy and/or partial cystectomy improve patients' quality of life by preserving their native bladder and sexual function without compromising oncological outcomes. Because a favorable response to chemoradiotherapy (CRT) is a prerequisite for successful bladder preservation, predicting and monitoring therapeutic response is an essential part of this approach. Diffusion-weighted magnetic resonance imaging (DW-MRI) is a functional imaging technique increasingly applied to various types of cancers. Contrast in this imaging technique derives from differences in the motion of water molecules among tissues and this information is useful in assessing the biological behavior of cancers. Promising results in predicting and monitoring the response to CRT have been reported in several types of cancers. Recently, growing evidence has emerged showing that DW-MRI can serve as an imaging biomarker in the management of bladder cancer. The qualitative analysis of DW-MRI can be applied to detecting cancerous lesion and monitoring the response to CRT. Furthermore, the potential role of quantitative analysis by evaluating apparent diffusion coefficient values has been shown in characterizing bladder cancer for biological aggressiveness and sensitivity to CRT. DW-MRI is a potentially useful tool for the management of bladder cancer, particularly in multimodal bladder-sparing approaches for MIBC.

Bone abnormal signal incidentally found in pre-biopsy diffusion-weighted MRI for suspected prostate cancer: what does it reflect?

OBJECTIVE: To clarify the clinical significance of incidentally found diffusion-weighted MRI (DW-MRI)-positive findings on pre-biopsy MRI in patients with suspected prostate cancer. PATIENTS AND METHODS: 754 consecutive patients with suspected prostate cancer underwent pelvic MRI including DW-MRI. 43 DW-MRI-positive bone lesions were found in 27 patients. Imaging findings of these lesions were compared with the clinical diagnosis. RESULTS: Of the 43 DW-MRI-positive bone lesions, 21 (48.8%) were diagnosed as metastatic prostate cancer. The remaining 22 (51.2%) were diagnosed as red bone marrow in 17, enchondroma in 1, ganglion in 1, osteoma in 1, fibrous dysplasia in 1 and bone infarction in 1. Enchondroma, ganglion, osteoma and fibrous dysplasia all showed T1-weighted imaging (T1WI) low and T2-weighted imaging (T2WI) high signals, while others, including prostate cancer metastases, showed T1WI and T2WI low signals. Of the 40 lesions with T1WI and T2WI low signals, metastatic prostate cancer had higher apparent diffusion coefficient values (median 0.42 × 10(-3) mm(2)/s) than other lesions (0.26 × 10(-3) mm(2)/s; p < 0.0001). CONCLUSIONS: DW-MRI-positive bone lesions represent various coexisting types of bone lesions, including metastatic cancer in patients with suspected prostate cancer. T2WI findings and apparent diffusion coefficient values can be helpful in diagnosing metastatic cancer.

Evaluation of indeterminate pulmonary nodules with dynamic MR imaging.

PURPOSE: We prospectively assessed whether enhancement characteristics on dynamic magnetic resonance (MR) imaging could distinguish indeterminate pulmonary nodules. METHODS: We evaluated 51 pulmonary nodules in 51 consecutive patients (11 female, 40 male; mean age, 64 years) using dynamic MR images acquired at 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 150, 180, 210, 240, 360, 480, 600, 720, and 840 s following injection of contrast material. We prospectively evaluated morphologic enhancement patterns, peak rate, time to peak enhancement, steepest slope, and washout of nodules and analyzed statistics to determine any differences between MR parameters, patient age, tumor size, and final diagnosis. RESULTS: We found 25 malignant, 12 active inflammatory, and 14 benign nodules. Nodule diameter was significantly larger for malignant than nonmalignant, and benign nodules (P≤0.01). Patients with malignant nodules were significantly older than those with nonmalignant (P=0.01) and active inflammatory (P=0.02) nodules. However, morphologic enhancement patterns, peak rate, time to peak enhancement, steepest slope, and washout characteristics at 2, 4, 8, and 12 min showed no significant difference between malignant and nonmalignant nodules and among malignant, active inflammatory, and benign nodules. CONCLUSION: Prospective assessment of dynamic MR images demonstrated their inadequacy for distinguishing indeterminate pulmonary nodules.

LSI-based amperometric sensor for bio-imaging and multi-point biosensing.

We have developed an LSI-based amperometric sensor called "Bio-LSI" with 400 measurement points as a platform for electrochemical bio-imaging and multi-point biosensing. The system is comprised of a 10.4 mm × 10.4 mm CMOS sensor chip with 20 × 20 unit cells, an external circuit box, a control unit for data acquisition, and a DC power box. Each unit cell of the chip contains an operational amplifier with a switched-capacitor type I-V converter for in-pixel signal amplification. We successfully realized a wide dynamic range from ±1 pA to ±100 nA with a well-organized circuit design and operating software. In particular, in-pixel signal amplification and an original program to control the signal read-out contribute to the lower detection limit and wide detection range of Bio-LSI. The spacial resolution is 250 µm and the temporal resolution is 18-125 ms/400 points, which depends on the desired current detection range. The coefficient of variance of the current for 400 points is within 5%. We also demonstrated the real-time imaging of a biological molecule using Bio-LSI. The LSI coated with an Os-HRP film was successfully applied to the monitoring of the changes of hydrogen peroxide concentration in a flow. The Os-HRP-coated LSI was spotted with glucose oxidase and used for bioelectrochemical imaging of the glucose oxidase (GOx)-catalyzed oxidation of glucose. Bio-LSI is a promising platform for a wide range of analytical fields, including diagnostics, environmental measurements and basic biochemistry.

Diffusion-weighted magnetic resonance imaging detection of renal cancer presenting with diffuse peritoneal metastases in a patient with hemodialysis-associated acquired cystic disease of the kidney.

A 59-year-old man was admitted with a large amount of ascites, cake-like omental thickening, and dialysis-associated acquired cystic disease of the kidney (ACDK). It was difficult to detect renal cancer, which was revealed as a primary site of peritoneal metastases by autopsy, with conventional cross-sectional imaging, such as enhanced computed tomography and T2, T1, and dynamic gadolinium-enhanced T1-weighted magnetic resonance imaging, because multiple renal cysts caused marked distortion of the renal parenchyma and the cancer had necrosis. We demonstrated the usefulness of diffusion-weighted imaging with a high b-factor to detect renal cancer presenting with peritoneal metastasis in a patient with ACDK.

Pulmonary emphysema: histopathologic correlation with minimum intensity projection imaging, high-resolution computed tomography, and pulmonary function test results.

OBJECTIVE: To prospectively evaluate the use of minimum-intensity projection (minIP) imaging, high-resolution (HR) computed tomography (CT), and pulmonary function tests for quantifying emphysema with histopathologic examination. METHODS: MinIP and HRCT imaging data (n = 23) were obtained, and relative areas of the lung with attenuation values below thresholds from -940 to -1000 Hounsfield units (HU) and first to 13th percentiles were calculated for both data. Pulmonary function tests were performed before lung resection. These parameters were compared with mean alveolar perimeters measured on resected samples. RESULTS: Strongest correlations with mean alveolar perimeter were obtained at -990 HU and the fifth percentile by minIP, -1000 HU and the seventh percentile by HRCT, and diffusion capacity. The correlation between the mean alveolar perimeter and relative areas below -990 HU by minIP showed significantly higher extension (0%-51%) than those below -1000 HU by HRCT (1%-21%). CONCLUSIONS: MinIP imaging is more than 2(1/2) times more predictive for quantifying emphysema than HRCT, although diffusion capacity of lung for carbon monoxide is also a valid index.

Can malignant and benign pulmonary nodules be differentiated with diffusion-weighted MRI?

OBJECTIVE: The objective of our study was to evaluate whether diffusion-weighted imaging (DWI) with a high b factor can be used to differentiate malignancies from benign pulmonary nodules. MATERIALS AND METHODS: This study included 54 pulmonary nodules (>or= 5 mm in diameter) in 51 consecutive patients (37 men, 14 women; mean age, 65.7 years; age range, 31-88 years). Thirty-six (67%) of the 54 pulmonary nodules were malignant, and 18 (33%) were benign. Two radiologists independently reviewed the signal intensity of the nodules on DWI with a b factor of 1,000 s/mm(2) using a 5-point rank scale without knowledge of clinical data. This scale was based on the following scores: 1, nearly no signal intensity; 2, signal intensity between 1 and 3; 3, signal intensity almost equal to that of the thoracic spinal cord; 4, higher signal intensity than that of the spinal cord; and 5, much higher signal intensity than that of the spinal cord. The Mann-Whitney U test and the receiver operating characteristic (ROC) curve were used to calculate the difference between the scores of malignant and benign nodules. RESULTS: On DWI, the mean score of malignant pulmonary nodules (4.03 +/- 1.16 [SD]) was significantly higher (p < 0.01) than that of benign nodules (2.50 +/- 1.47), with an area under the ROC curve of 0.796 (95% CI, 0.665-0.927). When a score of 3 was considered as a threshold, the sensitivity, specificity, and accuracy were 88.9% (95% CI, 78.6-99.2%), 61.1% (38.6-83.6%), and 79.6% (68.9-90.3%), respectively. Three small metastatic nodules (13, 16, and 20 mm) and one bronchioloalveolar carcinoma scored 1 or 2 on the 5-point rank scale. Three granulomas, two active inflammatory lung nodules, and one fibrous nodule scored 4 or 5. CONCLUSION: The signal intensity of pulmonary nodules may be useful for malignant and benign differentiation on DWI. However, the interpretation of small metastatic nodules, nonsolid adenocarcinoma, some granulomas, and active inflammatory nodules should be approached with caution.

Cine magnetic resonance imaging evaluation of peristalsis of small bowel with longitudinal ulcer in Crohn disease: preliminary results.

OBJECTIVE: To evaluate peristalsis of the small bowel with a longitudinal ulcer in Crohn disease using cine magnetic resonance imaging (MRI). METHODS: Fifteen patients with suspected or diagnosed Crohn disease were examined by cine MRI using a multislice and multiphase method. Inclusion criteria were pathological evidence of Crohn disease and confirmation of longitudinal ulceration in the small bowel by ileocolonoscopy, single- or double-contrast radiography of the small bowel, or surgery. Six of these patients were included in this study. Cine MRI findings of the small bowels were retrospectively reviewed by 2 radiologists. RESULTS: Asymmetric involvement or mesenteric rigidity with antimesenteric flexibility was seen in all patients by cine MRI. This finding was not seen in normal small bowel segments. A combination of ileocolonoscopy and contrast radiography detected longitudinal ulcers in 5 of the 6 patients, and surgery revealed ulceration in the remaining patient. CONCLUSIONS: Cine MRI was a feasible approach for detecting a longitudinal ulcer in small-bowel Crohn disease.

Sliding thin slab, minimum intensity projection imaging for objective analysis of emphysema.

PURPOSE: The aim of this study was to determine whether sliding thin slab, minimum intensity projection (STS-MinIP) imaging is more advantageous than thin-section computed tomography (CT) for detecting and assessing emphysema. MATERIALS AND METHODS: Objective quantification of emphysema by STS-MinIP and thin-section CT was defined as the percentage of area lower than the threshold in the lung section at the level of the aortic arch, tracheal carina, and 5 cm below the carina. Quantitative analysis in 100 subjects was performed and compared with pulmonary function test results. RESULTS: The ratio of the low attenuation area in the lung measured by STS-MinIP was significantly higher than that found by thin-section CT (P < 0.01). The difference between STS-MinIP and thin-section CT was statistically evident even for mild emphysema and increased depending on whether the low attenuation in the lung increased. Moreover, STS-MinIP showed a stronger regression relation with pulmonary function results than did thin-section CT (P < 0.01). CONCLUSION: STS-MinIP can be recommended as a new morphometric method for detecting and assessing the severity of emphysema.

Sliding thin slab, minimum intensity projection of the lung in asymptomatic subjects: lower limits of lung attenuation, without airways.

PURPOSE: A sliding thin slab, minimum intensity projection (STS-MinIP) is considered to be useful for detecting diseases that decrease lung attenuation. For evaluating these diseases, it would be useful to ascertain the lower limits of normal lung attenuation, allowing a division between normal and subnormal attenuation. However, normal lung attenuation may vary depending on respiratory status, anatomical position, and patient background factors. Our aim was to determine whether the lower limits of lung attenuation, without airways, in asymptomatic subjects using STS-MinIP varies under different conditions. MATERIALS AND METHODS: The study subjects were 43 volunteers without pulmonary symptoms. STS-MinIP was performed at full inspiration and full expiration at three levels of the lung. The lower limits of lung attenuation were compared among the three lung levels and between full inspiration and full expiration, the sexes, age groups, smokers and nonsmokers, and the right and left lungs. RESULTS: The lower limits of lung attenuation had significantly different Hounsfield unit values among lung levels, between the sexes at full inspiration, and between age groups at full expiration. CONCLUSION: This study shows that the lower limits of lung attenuation are influenced by lung fields, sex, and, on expiration, age.

CT-guided automated cutting needle biopsy by a combined method for accurate specific diagnosis of focal lung lesions.

PURPOSE: The purpose of our study was to evaluate a method of automated cutting needle biopsy (ACNB) that combines the use of a long-throw needle, higher mean number of needle passes, and tandem system, in terms of the accuracy of specific diagnosis of small and large lung lesions and the safety of the procedure. MATERIALS AND METHODS: Fifty-seven ACNBs were performed under computed tomography guidance using a tandem system with a 20-gauge and 18-gauge (through non-aerated lung) automated cutting needle with a throw length of 23 mm. We classified the nodules into 21 small nodules (< or =2 cm) and 36 large nodules (>2 cm). All ACNB diagnoses were divided into three groups: specific, non-specific, and false diagnoses. All of the complications were recorded. RESULTS: The mean number of ACNB specimens obtained was 2.0. Of the 35 ACNB procedures for malignant lesions, 33 yielded a specific malignant diagnosis (33/35, 94%). Of the 22 procedures for benign lesions, 17 gave a specific benign diagnosis (17/22, 77%). The diagnostic accuracy for small nodules was no lower than that for large nodules. Postbiopsy pneumothorax occurred in 18 patients (32%). CONCLUSION: The diagnostic accuracy of the combined method is as high for small lung nodules as for large ones. The procedure has high diagnostic accuracy for the subtypes of lung cancer and an acceptable complication rate.