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Various methods for evaluating bone mineral in appendicular, and axial bone or in the whole skeleton have recently become available. As bone mineral is one of the major determinants of bone strength, its exact measurement should be useful for the diagnosis of osteoporosis, as well as for the prediction of fracture risk and monitoring of therapeutical response. The aims of this paper are to review the fundamental performance of bone mineral measurements, the improvements in DXA systems, and the progress in site-specific bone mineral instruments for the radius and calcaneus used in Japan, and to introduce diagnostic criteria for primary osteoporosis, and report on annual rates of bone loss in Japanese females.

From October 1987 to September 1989, 29 patients with newly diagnosed immunoglobulin A nephropathy underwent renal gallium 67 scintigraphy. The radioisotope uptake ratio between left kidney and soft tissue was measured 48 hours after bolus injection of gallium 67. In 25 patients the ratio ranged from 1.30 to 3.56 (mean, 1.95 +/- 0.47). Ratios were not obtained in four patients because strong gastrointestinal isotope excretion. Plots of reciprocal serum creatinine concentration against time and Kaplan-Meier plots of renal survival were used to assess the predictive value of the test in 20 patients for whom long-term follow-up data were available. The radioisotope uptake ratio was negatively correlated with the slope of reciprocal serum creatinine against time (r = -0.64, P0.01). When the 20 patients were divided into two groups according to radioisotope uptake ratio (group A, ratio1.95, nine patients; group B, ratio1.95, 11 patients), life table analysis of renal survival showed group B to have a better prognosis than group A (P0.05). The results indicate that increased renal gallium uptake is predictive of a poor prognosis in patients with immunoglobulin A nephropathy.

In this paper we described the relation between serum bone metabolic markers and bone mineral densities (BMD) in both cortical bone and trabecular bone in 22 patients with primary hyperparathyroidism (PHP) and in 108 patients with renal hyperparathyroidism (RHP). As bone formation markers, total alkaline phosphatase (AlP), intact osteocalcin and the carboxyterminal propetide of type I procollagen (PICP) were measured. As bone resorption markers, the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRACP) were measured. BMDs in the mid-radius and lumbar vertebrae (L2–4) were assessed using dual energy X-ray absorptiometry. Among the bone formation markers, the serum levels of AlP and and osteocalcin seemed to reflect osteoblast activity more accurately than PICP. Regarding the bone resorption markers, the serum levels of ICTP seemed to reflect osteoclast function more adequately than TRACP. In both PHP and RHP patients, the decrease in R-BMD was more prominent than that in L-BMD. In RHP patients, the decrease in BMDs, especially those of the midradius, negatively correlated with both bone formation markers and bone resorption markers. We concluded that the excessive PTH secretion elevates both the markers of bone formation and resorption, and that BMD decreases more significantly in cortical bone than in trabecular bone. Measurements of bone metabolic markers may prove to be useful for predicting bone loss in hyperparathyroidism.

Coronary vasomotor response might be impaired in metabolic syndrome (MS); however, the precise abnormality has not been elucidated. The aim of this study was to assess coronary-vasomotor response in MS subjects using N-13 labeled ammonia and positron emission tomography.Myocardial blood flow (MBF) was measured at rest and during adenosine infusion in MS subjects (n = 13, MS group) with no definite evidence of heart disease and in subjects without MS (n = 14, non-MS group). Coronary vascular resistance (CVR) was calculated by dividing the mean aortic blood pressure by MBF. Myocardial blood flow reserve (MFR) was calculated as the ratio of the MBF during adenosine infusion to that during rest. Blood chemical parameters were measured to evaluate their relationship with MFR. During adenosine infusion, MBF was lower (p = 0.0085) and CVR higher (p = 0.0128) in the MS group than in the non-MS group and MFR was significantly lower in the MS group than in the non-MS group (2.13 +/- 0.99 vs. 3.38 +/- 0.95, p = 0.0027). Multivariate analysis demonstrated that the homeostasis model assessment-insulin resistance (p0.05) and the presence of hypertension (p0.05) were independent determinants of MFR.The results indicate that MFR was impaired in MS subjects, suggesting that an abnormal coronary microvascular response occurred in these subjects. This abnormality may have been partially due to insulin resistance and hypertension.

In this paper we propose a new metric of SRAM cell stability named static cell-flip voltage (SCFV). In order to measure SCFV, novel design-for-test (DFT) techniques with asymmetric cell-bias-voltage modulation (ACBVM) are introduced, in which the cell-data retention is measured with sweeping potential of a ground node connected to one of the cross-coupled invertors of a cell and source voltage of PMOS loads swept. It is shown that SCFV has high correlation with conventional static noise margin (SNM). The proposed techniques make it possible to directly obtain large amounts of stability data of memory cells arranged in matrix for an SRAM macro, which has been difficult with conventional SNM measurements. The measured data of 1 Kb SRAM with 65 nm technology show good correspondence with simulated results.

Embedded DRAMs have superior features for applications that require very high memory bandwidth, such as graphics and multimedia. To achieve high memory bandwidth, various techniques such as widening input/output pins shrinking the unit array size, and performing a read operation and a write operation concurrently have been reported. However, these embedded DRAM macros incur considerable area penalty to obtain high memory bandwidth. Among the techniques for achieving high bandwidth, the concurrent read/write operation is a very effective method in performing a read-modify-write function and a double-buffer function for the graphics applications. A pseudo-two-port embedded DRAM macro that performs concurrent read/write operations at high frequency without sacrificing cell efficiency is reported in this paper. To accomplish this, a read/write cross-point switch circuit (RWCC) and distributed steering redundancy switches (DSRS) are introduced. A 32 Mb macro is characterized via a test-chip fabricated in a 65 nm embedded DRAM process.

A single-power supply 64 kB SRAM is fabricated in a 45 nm bulk CMOS technology. The SRAM operates at 1GHz with a 0.7 V supply using a fine-grained bitline segmentation architecture and with an asymmetrical unit-ratio 6T cell. With the asymmetrical cell, 22% cell area has been saved compared to a conventional symmetrical cell. This bulk SRAM is designed for GHz-class sub-lV operation.

A power reduction technique is proposed for SRAM macros in which dual power supply scheme is combined with dynamic voltage scaling scheme. The test chip with 1Mb SRAM macro fabricated using 65nm CMOS process has demonstrated that the active power in low power mode is reduced by 25% compared to that of the conventional scheme. The leakage current at sleep mode is also decreased by three orders of magnitude compared to that of the conventional one.

The purpose of this study was to determine the best bed overlaps in PET/CT 3D acquisition to reconstruct a transverse image with uniform quality not depending on axial slice position. First, the value of the image contrast ratio, non-uniformity (NU) value, and coefficient of variation (COV) were examined in the image of a cylindrical phantom at each slice position. The image-contrast ratio was almost constant in all slice images, and the NU value and COV were also constant in the slice images up to 13 and 19 slices from the center, respectively, but these values increased with closeness to the edge of the detector. Secondly, COV and image contrast ratios at different sizes of (18)F-FDG concentration (phi 19 mm, phi 16 mm, phi 13 mm, phi 10 mm) were examined in the case of overlapping the bed frame with 11, 15, and 21 slices in acquiring data in 3D mode. In 21 and 15 slices overlapping in acquisition, the image contrast ratios for all concentrations were greater than 0.13, which was the threshold image contrast ratio needed to identify FDG concentration from the background image with naked eye scanning under our conditions. However, in 11 slices with overlapping acquisition, the image-contrast ratio for a phi 10 mm concentration were close to or less than 0.13 in the all slice images. As a result, 15 overlapping slices was a reasonable minimum number of slices to identify a phi 10 mm (18)F-FDG concentration while maintaining the image quality in PET/CT 3D acquisition in our institution.

DFT techniques to implement ECC circuitry on memory macro with no additional test cost are proposed. New methodology to design a Hamming code matrix is used to achieve whole ECC system testing with standard memory BIST and conventional test sequence. The proposed ECC techniques are implemented in a 512Kb SRAM macro and demonstrated by hardware characterization with 90nm technology.

The growth of mobile equipment market is spurring demand for low-power SRAM macros. For mobile applications, in particular, there is a need to reduce standby current leakage while keeping memory cell data. For this purpose, several techniques have been reported. They introduce reduction of cell bias voltage in standby state, but the cell bias level is determined by Vth and supply voltage as described later. In 90nm technology and beyond, fluctuation of Vth is increasing and leakage reduction efficiency of these techniques is greatly affected. Therefore, a cell leakage reduction technique immune to process and/or environment fluctuations is required. In addition, leakage reduction in row decoder circuit is also desirable, because standby current leakage in peripheral circuits is dominated by row decoders. In order to meet these requirements, a novel cell bias control technique and a novel row decoder circuit are proposed. We fabricated a 90nm 512Kb low leakage SRAM macro.

Design-for-test (DFT) techniques for acquiring at-speed function fail bit maps with conventional wafer test equipment are proposed. The SRAM core is operated with a high frequency clock generated by a gain-suppressed VCO which can reduce clock jitter. The data are output with a data out strobe control circuit synchronizing with an external low frequency clock. Using these techniques, the SRAM chip appears to be operating with a low frequency tester clock while the SRAM core is operated with a high frequency internal clock. Therefore, a fail bit map at high frequency operation can be obtained with conventional wafer test equipment. The at-speed test with fail bit map acquisition allows slow bit cell replacement to spare cell or chip-by-chip internal timing optimization with fuse-blowing. It results in a drastic reduction in test cost and performance yield improvement.

A double data rate (DDR) SRAM bus architecture which can eliminate any speed penalty for doubling the I/O frequency and support single data rate (SDR) compatibility has been proposed. A method to guarantee data coherency for both DDR and SDR has also been described. With this architecture, we developed a 4.5 Mb DDR SRAM. Under the typical 2.5 V condition, a 600 MHz I/O frequency was achieved.

In view of the remarkable progress in MPU performance, improvement in the data rate of L2 cache SRAMs is desirable to maximize system performance. As a solution, Double-Data-Rate (DDR) SRAMs, which can realize an I/O frequency of up to twice that of conventional Single-Data-Rate (SDR) SRAMs, have been reported. Increase in operation-current due to higher operation frequency causes severe power-line noise and heating. Therefore, reduction of operation-current is an important issue in designing high-speed SRAMs. In order to realize both high-frequency operation and power reduction, we propose new sense circuitry and a bit-line load scheme.

In order to exclude the metabolically less-active cortical bone in the posterior portion of the lumbar spine, and to exclude the calcification of abdominal aorta which frepuently occurs in elderly persons, both of which are included in the conventional anteroposterior (AP) bone mineral determinations, clinical interest has been directed toward lateral scanning. In this paper, the performance and clinical application of lateral scanning with dual energy X-ray absorptiometry (DEXA) have been reviewed. The precision, estimated as the reproducibility of measurements, of lateral bone mineral density (BMD), is inferior to that of AP-BMD (N=5, C.V. 5.57% vs 1.80%). With lateral scanning, the distributions of bone mineral within the vertebral body was different. The highest BMD was observed in the posterior inferior portion (100%), followed by the posterior superior (89%), anterior inferior (77%), and anterior superior portions (65%). In lateral scans, BMD within the region of interest (ROI) containing the shell, composed of cortical bone, is higher than BMD within the ROI without the shell (N=28, 87.8±5.9% for shell (+) vs 81.5±10.3% for shell (−), p

Many bone measurement techniques have been developed and used in the early detection of bone loss, the prediction of fracture, and the monitoring of therapeutical responses in osteoporosis. Each technique has its own principle and fundamental features such as the site of measurement (e.g., appendicular or axial bone), precision, accuracy, spatial resolution, data-acquisition time, and radiation dose. Each also differs in its performance in the clinical practice of osteoporosis. The purpose of this chapter is to review the present state and future prospects for the use of bone mass measurements clinically.

Widely used for cerebral perfusion imaging, I-123 iodoamphetamine (I-123 IMP) is also known to accumulate in malignant melanomas. A case of malignant melanoma is presented, in which I-123 IMP scintigraphy was useful to visualize the bone metastases. During the period of postoperative follow-up, multiple foci of increased I-123 IMP uptake appeared in the skeleton. Conventional bone scintigraphy was less striking, showing cold defects or irregular radionuclide uptake.

The effects of recreational exercise and milk intake on BMD were assessed in Japanese men using analysis of covariance with significant predictor variables, selected from age, height, body weight and body mass index (BMI), as covariates. The influence of degenerative vertebral changes on these effects was also evaluated. Recreational exercise was found to be positively associated with BMD at the lumbar spine and the femoral neck, whereas milk intake, a possible indicator of calcium intake in the Japanese, was positively associated with BMD at the radius and the lumbar spine. Not only vertebral BMD but also radial and femoral neck BMD was higher in the subjects with osteophytosis or sclerosis in the lumbar vertebrae. Neither exercise nor lumbar pain was significantly related to these vertebral changes. These data suggest a protective effect of regular recreational exercise and milk intake on bone health in Japanese men.

To evaluate bone metastasis from hepatocellular carcinoma (HCC), both bone and 99mTc-HM-PAO scintigraphies were performed in six patients with clinically and pathologically confirmed HCC. Two patients had a bone scintigram which revealed abnormal accumulation in the skull base, pelvic bone and thoracic spine. The 99mTc-HM-PAO scans of both these patients also showed abnormal accumulation in the same sites. The bone scintigrams in one patient revealed not only abnormal accumulation in the ribs but also photon deficient areas in the sternum, thoracic spine and femur, while 99mTc-HM-PAO scans showed abnormal accumulation in all these sites. In three patients, bone scintigraphy revealed photon deficient areas in the ribs, pelvic bone and femur, and their 99mTc-HM-PAO scintigrams showed abnormal accumulation in the same sites. Thus, it was shown that, in the detection of bone metastasis from HCC by means of bone scintigraphy, it was necessary to pay attention to hot and cold lesions, and that a combination study with 99mTc-phosphorous compounds and 99mTc-HM-PAO was useful in evaluating these lesions.

Squamous cell carcinoma (scc) is the most frequently type of oral cancer, but no reliable specific tumor markers of scc have been obtained. In this paper, the authors applied measurement of squamous cell carcinoma related antigen (scc antigen), a useful tumor marker of scc of the uterine cervix, to oral cancer patients and evaluated the clinical values of scc assay in diagnosis, follow-up and prognosis.The subjects were 29 cases of oral cancer and 23 cases of benign oral disease. The oral cancer cases included 12 cases of tongue cancer, 5 of buccal cancer, 4 of gingival cancer, 2 of cancer of the oral floor, 2 of cancer of the maxillary sinus and 4 cases of other cancers. Twenty one of these cases (about 72%) were histologically scc.Serum scc antigen levels were determined by the RIA KIT employing 125 I-labelled scc antigen as tracer. The cut off level was set as 2.3ng/ml.The following results were obtained.1) The subjects with oral cancer exhibited a higher scc antigen level than those of patients with non-bearing oral cancer or those of cases with benign oral diseases.2) The positive rate of the subjects with oral cancer was relatively high and 44% were at a level over 2.3ng/ml. Particularly in scc, 60% were at a level over 2.3ng/ml. Among 16 subjects with non-bearing oral cancer, on the other hand, only one subject showed positive. All subjects with benign oral disease were within normal range.3) As to the regions of oral cancer, tongue cancer and cancer of the oral floor showed relatively high scc antigen levels.4) There was no relationship between stages and scc antigen levels.5) Post-treatment scc antigen levels tended to decrease to within normal range in cases where the disease followed a good course, while they tended to increase in those that followed a poor course.6) The measurement of scc antigen levels appears to be especially useful for diagnosis, follw-up and evaluating prognosis in oral squamous cell carcinoma.

The usefulness of bone scintigraphy using 99m-Tc-labeled phosphorous compounds was evaluated in 134 of 234 patients with cancers of the head and neck who were treated between June 1975 and March 1985.The overall positive rate in bone scintigraphy was 49%, but the true-positive rate was 25%. Distant bone metastases were found in 18% of the patients. Fifty-five per cent in the patients with true-positive bone scintigraphy had positive x-ray findings. The most common sites of distant bone metastases in head and neck cancers were the rib and the thoracic vertebrae. The rate of distant metastases increased with the T-classification. No relation was observed between bone scintigraphy and serum alkaline phosphatase activity.In conclusion, bone scintigraphy with 99m-Tc-diphosphonate was found to be very useful in detecting early bone metastases.

Using in vivo and in vitro experimental models, the uptake and excretion of 67Ga-citrate in tumor cells and normal cells were studied. The time-lapse accumulation of 67Ga in the tumor of rats bearing Yoshida sarcoma reached its peak 24 h after the administration of 67Ga and gradually decreased thereafter. However, the excretion of 67Ga from the tumor was less than that from normal lung. For culture cells in vitro, the uptake of 67Ga increased with lapse of contact time between 67Ga and the cells, but there was no distinct difference between the results for tumor cells and normal skin fibroblasts. The excretion of 67Ga from the cells tended to decrease with prolongation of the contact time, the excretion from tumor cells being only about 10% after a contact time of 24 h. This indicated a significant delay in excretion in comparison with that of normal skin fibroblasts. This delay in the excretion of 67Ga may be an important factor in the tumor accumulation of 67Ga.

To improve the scintigraphic differential diagnosis of thyroid nodules, Tc-99m pertechnetate-Tl-201 Cl subtraction scintigraphy (Tc-Tl subtraction scanning) was performed in 106 patients with various histologically proven thyroid nodules. Results were evaluated by comparison with surgical findings and preoperative ultrasonographic results. Thyroid nodules were more successfully detected by Tc-Tl subtraction scanning than by either Tc-99m pertechnetate or Tl-201 Cl scintigraphy alone. Detection of nodules was further improved when images recorded by the three methods were integrally observed (sensitivity 83%, accuracy 89%), with detectability approaching that of ultrasonography. False-positive or -negative Tc-Tl subtraction scans were obtained principally when multiple nodules were present (7 cases) or when no discrepancy existed between the accumulations of Tc-99m pertechnetate and Tl-201 Cl (18 cases). Most colloid nodules exhibited irregular margins, heterogeneous internal accumulations of Tl-201 Cl, and distorted shapes on Tc-Tl subtraction scans, while the majority of adenoma were oval-shaped with smooth margins. Carcinoma were characterized by homogeneous internal accumulation of Tl-201 Cl and distorted shapes.

Two patients with polymyositis showed abnormal muscular uptake of Tc-99m-methylene diphosphonate (MDP) during routine bone imaging. Imaging with Tc-99m MDP is a useful tool in monitoring the activity of the diseased muscle.

A newly developed dual photon absorptiometry system (DCS-600, ALOKA Co., LTD.) using two monochromatic X-rays for the determination of bone mineral in the peripheral bone was fundamentally studied, in comparison to single photon absorptiometry system (SPA). The accuracy and precision in DCS-600 were equal to or better than SPA system. Furthermore, in DCS-600 the forearm could be imaged, and the manipulation was easy. Thus DCS-600 was found to be a good instrument as a quantifying system of bone mass.

A parathyroid adenoma imaged by Ga-67 citrate in a 17-year-old man with primary hyperparathyroidism and a palpable solid tumor in the neck is presented. Although preoperative examination and intraoperative findings suggested a parathyroid carcinoma, histologic studies showed a parathyroid adenoma with predominant chief cell type.

The degree of deposition of small-particle colloids such as 99mTc-antimony sulfide colloids (ASC-group) and 99mTc-rhenium colloid (Tc-Re) in the bone marrow and lymph node was studied. H-ASC that was prepared in our laboratory was concentrated to a higher degree both in the bone marrow and lymph nodes, compared with other colloids. The H-ASC were mostly from 5 to 12.5 nm and the shape was uniform and spherical. The degree of deposition of Tc-Re in rabbit lymph nodes was not higher, however, the label was considered to be valuable clinically. The degree of deposition of Tc-Re in the bone marrow was not satisfactory. The size of Tc-Re was much smaller than H-ASC, ranging from 3 to 5 nm. From these results, it is considered that factors affecting deposition in the marrow are not identical to those in the lymph nodes.