MR guided focused ultrasound: technical acceptance measures for a clinical system

Magnetic resonance (MR) guided focused ultrasound (MRgFUS) is a hybrid technique which offers efficient and safe focused ultrasound (FUS) treatments of uterine fibroids under MR guidance and monitoring. As a therapy device, MRgFUS requires systematic testing over a wide range of operational parameters prior to use in the clinical environment. We present technical acceptance tests and data for the first clinical MRgFUS system, ExAblate 2000 (InSightec Inc., Haifa, Israel), that has been FDA approved for treating uterine fibroids. These tests characterize MRgFUS by employing MR temperature measurements in tissue mimicking phantoms. The coronal scan plane is empirically demonstrated to be most reliable for measuring temperature elevations resulting from high intensity ultrasound (US) pulses ('sonications') and shows high sensitivity to changes in sonication parameters. Temperatures measured in the coronal plane were used as a measure of US energy deposited within the focal spot for a range of sonication parameters used in clinical treatments: spot type, spot length, output power, sonication duration, US frequency, and depth of sonication. In addition, MR images acquired during sonications were used to measure effective diameters and lengths of available sonication spot types and lengths. At a constant 60 W output power, the effective spot type diameters were measured to vary between 4.7 +/- 0.3 mm and 6.6 +/- 0.4 mm; treatment temperatures were found to decrease with increasing spot diameter. Prescribing different spot lengths was found to have no effect on the measured length or on measured temperatures. Tests of MRgFUS positioning accuracy determined errors in the direction parallel to the propagation of the US beam to be significantly greater than those in the perpendicular direction; most sonication spots were erroneously positioned towards the FUS transducer. The tests reported here have been demonstrated to be sufficiently sensitive to detect water leakage inside the FUS transducer. The data presented could be used for comparison by those conducting acceptance tests on other clinical MRgFUS systems.     

Terminal osseous dysplasia with pigmentary defects: clinical description of a new family

Terminal osseous dysplasia with pigmentary defects is an extremely rare condition characterized by the triad of pigmentary anomalies of the skin, skeletal abnormalities of the limbs and recurring digital fibromatosis of childhood, with considerable interfamilial and intrafamilial variability of expression. It has recently been added to the small group of X-linked dominant disorder with prenatal male lethality on the basis of a four-generation pedigree in which only females were affected, male progeny was decreased and the number of spontaneous abortions was increased. In this clinical report, we describe a 2-year-old girl with full expression of the syndrome including skin defects, skeletal anomalies and recurrent fibromatosis of fingers and toes and her mother who presents with only multiple hypertrophic oral frenula. As previously demonstrated, our patients also show an extremely skewed X-inactivation on blood cells, strongly suggesting that there is selective disadvantage for cells carrying the mutated gene on their active X chromosome. Terminal osseous dysplasia with pigmentary defects could represent an additional example of extreme intrafamilial variability as already described for other X-linked dominant disorders.     

Quality assurance and system stability of a clinical MRI-guided focused ultrasound system: four-year experience

To retrospectively evaluate the four-year experience of a quality assurance method for a MRI-guided focused ultrasound system that uses temperature maps acquired during heating in an ultrasound/MRI phantom. This quality assurance method was performed before 148 clinical uterine fibroid thermal ablation treatments. The stability of the peak temperature rise, the targeting accuracy, the shape of the heated zone, and the noise level in the imaging was evaluated. The peak temperature rise was mostly stable for the first three years. An increase in heating was observed when the system was replaced after year three. Detection of this increase was taken into account in the subsequent clinical treatments. A small secondary hotspot was detected by the temperature maps and was seen to be resolved after system calibration. The average standard deviation in unheated regions of the phantom in the temperature maps was 0.5 +/- 0.2 degrees C; it was less than 1 degrees C in all but one procedure. The average initial targeting error was 2.8 +/- 1.8 and 2.8 +/- 2.1 mm in two radial directions and 7.7 +/- 2.9 mm along the ultrasound beam direction. The width of the heating profile was consistent over the four years. This simple method to evaluate the performance appeared to be sensitive to small changes in system performance, which was adequately stable over a four-year time period.     

Proteinuria selectivity: description of a new index

An improved simple method for determination of selectivity index has been described. This new index (Creteil index) has been compared to Cameron index. The correlation between both indexes has been 0.949 (R-squared). Creteil index is a less expensive method because only two determinations are requisited in serum and urine: albumin and IgG. In Cameron index, transferrin and IgG are detected and albumin has to be measured in addition in the blood to appreciate the nephrotic syndrome.     

Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

Background  

Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap.     

Hepatitis-associated aplastic anemia: description of a new case

Hepatitis-associated aplastic anemia is an only recently recognised syndrome. We present a case whereby a month after an episode of fever, a 17-year-old boy was recovered with liver enzyme elevation and circulating platelet reduction. All the acute viral hepatitis markers were negative. After bone marrow aspiration a severe aplastic anemia was diagnosed and all the findings were consistent with hepatitis-associated aplastic anemia. The disorder was initially treated with glucocorticoids and platelet transfusion, obtaining the normalization of the liver enzymes but worsening of the aplastic anemia. An HLA-identical related marrow donor was not found. The patient responded to immunosuppressive treatment but died of multi-organ failure due to severe sepsis.     

Hemifacial myohyperplasia: description of a new syndrome.

Hemifacial hypertrophy is a rare condition characterized by unilateral enlargement of all tissues of the face. We describe three patients who exhibit hemifacial hyperplasia of the muscles of facial expression with no other organ system involvement. These three cases, in addition to six other cases identified in the literature, describe a unique constellation of characteristics that place these patients into a distinct syndrome. We suggest that the term "hemifacial myohyperplasia" be used to describe this specific and unique condition.     

一种新型自适应动态滤波器在超声成像中的应用

目的 为使动态滤波器的中心频率可实时匹配回波信号中心频率,本文设计了一种新型的自适应动态滤波器.方法 本文自适应机制是以快速傅里叶变换（fast Fourier transform,FFT）算法实时分析真实回波信号的频率特性,根据频率编号自适应匹配动态滤波器的系数.该滤波器的所有模块基于现场可编程门阵列（field programmable gate array,FPGA）硬件实现,最后将加入白噪声的正弦信号使用Modelsim时序仿真工具进行仿真.结果 仿真结果表明,这种滤波器能良好匹配回波信号中心频率,消除噪声.结论 本文提出的自适应动态滤波器满足高速实时系统的要求,为超声系统中滤波器的设计提供了可靠依据.     

Severity score system for progressive myelopathy: development and validation of a new clinical scale

Progressive myelopathies can be secondary to inborn errors of metabolism (IEM) such as mucopolysaccharidosis, mucolipidosis, and adrenomyeloneuropathy. The available scale, Japanese Orthopaedic Association (JOA) score, was validated only for degenerative vertebral diseases. Our objective is to propose and validate a new scale addressing progressive myelopathies and to present validating data for JOA in these diseases. A new scale, Severity Score System for Progressive Myelopathy (SSPROM), was constructed covering motor disability, sphincter dysfunction, spasticity, and sensory losses. Inter-and intra-rater reliabilities were measured. External validation was tested by applying JOA, the Expanded Disability Status Scale (EDSS), the Barthel index, and the Osame Motor Disability Score. Thirty-eight patients, 17 with adrenomyeloneuropathy, 3 with mucopolysaccharidosis I, 3 with mucopolysaccharidosis IV, 2 with mucopolysaccharidosis VI, 2 with mucolipidosis, and 11 with human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy participated in the study. The mean ± SD SSPROM and JOA scores were 74.6 ± 11.4 and 12.4 ± 2.3, respectively. Construct validity for SSPROM (JOA: r = 0.84, P < 0.0001; EDSS: r = −0.83, P < 0.0001; Barthel: r = 0.56, P < 0.002; Osame: r = −0.94, P < 0.0001) and reliability (intra-rater: r = 0.83, P < 0.0001; inter-rater: r = 0.94, P < 0.0001) were demonstrated. The metric properties of JOA were similar to those found in SSPROM. Several clinimetric requirements were met for both SSPROM and JOA scales. Since SSPROM has a wider range, it should be useful for follow-up studies on IEM myelopathies.     

The dosimetric properties of an intraoperative radiation therapy applicator system for a Mevatron-80

An applicator system for intraoperative radiation therapy has been fabricated which does not require physical docking with the accelerator. A dosimetric study has been completed which documents the properties of this system for a variety of electron beam energies, applicator sizes, collimator settings, both primary and secondary, and source-surface distance (SSD) settings. Sensitivity of the system to common misalignment errors was also determined. Results indicate (a) applicator leakage of less than 5%, (b) beam flatness to within plus or minus 5% at the dMAX with a single primary collimator setting, (c) smooth changes in output with cone size, beam energy and SSD, and (d) negligible changes in dose distributions within alignment errors permitted by the system.     

The histological features of microwave coagulation therapy: an assessment of a new applicator design

Microwave ablation of tumours within the liver may become an adjunct or alternative to resection in patients with primary or secondary cancers. This technique combines the benefits of a large, localized coagulative effect with a single insertion of the applicator, in a significantly shorter time than comparable treatments. A new range of microwave applicators were developed and tested in animal models and both ex-vivo and in-vivo specimens of human liver at resection. At laparotomy, the applicator tip was inserted into normal liver parenchyma and tumours, with each specimen subjected to irradiation for 180 s or more and at varying power outputs. On sectioning an area of spherical blanching was observed around the applicator cavity. Microscopically a zone of coagulative necrosis was seen adjacent to the site of probe insertion. Damage to blood vessels and bile ducts occurred distal to the probe cavity suggesting the passage of heated fluid, a finding that was diminished by temporary occlusion of the hepatic vasculature (a Pringle manoeuvre). Ultra-structural damage was confirmed within the burn zone and selected liver enzymes were shown to be functioning beyond this region. We suggest this indicates the surrounding liver parenchyma is functioning normally and therefore the volume of microwave-induced damage is controllable. We are confident that the new applicator design will allow the effective treatment of larger tumours in a safe and controlled manner with a single application of energy.     

Real-time photoacoustic imaging of prostate brachytherapy seeds using a clinical ultrasound system

Prostate brachytherapy is a popular prostate cancer treatment option that involves the permanent implantation of radioactive seeds into the prostate. However, contemporary brachytherapy procedure is limited by the lack of an imaging system that can provide real-time seed-position feedback. While many other imaging systems have been proposed, photoacoustic imaging has emerged as a potential ideal modality to address this need, since it could easily be incorporated into the current ultrasound system used in the operating room. We present such a photoacoustic imaging system built around a clinical ultrasound system to achieve the task of visualizing and localizing seeds. We performed several experiments to analyze the effects of various parameters on the appearance of brachytherapy seeds in photoacoustic images. We also imaged multiple seeds in an ex vivo dog prostate phantom to demonstrate the possibility of using this system in a clinical setting. Although still in its infancy, these initial results of a photoacoustic imaging system for the application of prostate brachytherapy seed localization are highly promising.     

Hemilaminectomy for removal of extramedullary or extradural spinal cord tumors: medium to long-term clinical outcomes

Purpose

Laminectomy is generally the treatment of choice for removal of spinal tumors. However, it has been shown that laminectomy may cause instability due to damage of posterior elements of the spinal column, which may induce subsequent kyphosis in the future. Therefore, to reduce the risk of deformity and spinal instability after laminectomy, hemilaminectomy has been used. However, the medium to long-term effects of hemilaminectomy on spinal sagittal alignment is not well understood. The present study was performed to evaluate the clinical outcomes, including spinal sagittal alignment of patients, associated with spinal cord tumors treated by surgical excision using hemilaminectomy.

Materials and Methods

Twenty hemilaminectomy operations at our institute for extramedullary or extradural spinal cord tumors in 19 patients were evaluated retrospectively with an average follow-up of 85 months (range, 40-131 months). Neurological condition was evaluated using the improvement ratio of the Japanese Orthopaedic Association Score (JOA score) for cervical, thoracic myelopathy, or back pain, and sagittal alignment by sagittal Cobb angle of the hemilaminectomied area.

Results

The mean improvement ratio of neurological results was 56.7% in the cervical spine (p < 0.01, n = 10), 26.3% in the thoracic spine (not significant, n = 5), and 48.6% in the lumbar spine (NS, n = 5). The sagittal Cobb angle was 4.3 ± 18.0° in the preoperative period and 5.4 ± 17.6° at the latest follow-up, indicating no significant deterioration.

Conclusion

Hemilaminectomy is useful for extramedullary or extradural spinal cord tumors in providing fair neurological status and restoration of spinal sagittal alignment in medium to long-term follow-up.     

Autophagy in brain tumors: a new target for therapeutic intervention

The role of autophagy, traditionally considered a cellular homeostatic and recycling mechanism, has expanded dramatically to include an involvement in discrete stages of tumor initiation and development. Gliomas are the most aggressive and also the most common brain malignancies. Current treatment modalities have only a modest effect on patient outcomes. Resistance to apoptosis, a hallmark of most cancers, has driven the search for novel targets in cancer therapy. The autophagy lysosomal pathway is one such target that is being explored in multiple cancers including gliomas and is a promising avenue for further therapeutic development. This review summarizes our current understanding of the autophagic process and its potential utility as a target for glioma therapy.     

Use of splenic ultrasound: a new wave for immune thrombocytopenic purpura.

AIMS--To examine whether a therapeutic dose of ultrasound waves, when directed through the thoracic wall to the spleen, would significantly affect the platelet count in patients with stable immune thrombocytopenic purpura (ITP). METHODS--Continuous ultrasound at 1 W/cm2 spatial average-time average (SATA) intensity for up to one minute/5 cm2 treatment field was well tolerated in 13 patients with ITP and one with non-Hodgkin's lymphoma. Five healthy controls were also similarly treated. Peak platelet increments occurred four to eight hours after ultrasound treatment in the ITP group (n = 16 treatments). RESULTS--The mean peak platelet increment was 6.25 x 10(9)/l with a 5% confidence interval of the mean (95% CI) of 3.32 to 8.93 x 10(9)/l (p = 0.0004). The mean peak platelet increment of normal controls was 6.6 (n = 5; 95% CI = -2.3 to 15.5; p = 0.21) and for sham treated patients it was 0.66 (n = 11; 95% CI = -1.5 to 2.8; p = 0.60). There was a significant inverse correlation between patient age in the ITP group and peak platelet increment (r = -0.60; p = 0.015). CONCLUSIONS--Splenic ultrasound is a novel approach to the treatment of ITP, and may find a place in its diagnosis or management.