Ultrasound image based visual servoing for moving target ablation by high intensity focused ultrasound

Background

Although high intensity focused ultrasound (HIFU) is a promising technology for tumor treatment, a moving abdominal target is still a challenge in current HIFU systems. In particular, respiratory‐induced organ motion can reduce the treatment efficiency and negatively influence the treatment result. In this research, we present: (1) a methodology for integration of ultrasound (US) image based visual servoing in a HIFU system; and (2) the experimental results obtained using the developed system.

Materials and methods

In the visual servoing system, target motion is monitored by biplane US imaging and tracked in real time (40 Hz) by registration with a preoperative 3D model. The distance between the target and the current HIFU focal position is calculated in every US frame and a three‐axis robot physically compensates for differences. Because simultaneous HIFU irradiation disturbs US target imaging, a sophisticated interlacing strategy was constructed.

Results

In the experiments, respiratory‐induced organ motion was simulated in a water tank with a linear actuator and kidney‐shaped phantom model. Motion compensation with HIFU irradiation was applied to the moving phantom model. Based on the experimental results, visual servoing exhibited a motion compensation accuracy of 1.7 mm (RMS) on average. Moreover, the integrated system could make a spherical HIFU‐ablated lesion in the desired position of the respiratory‐moving phantom model.

Conclusions

We have demonstrated the feasibility of our US image based visual servoing technique in a HIFU system for moving target treatment.     

Sequence tagged sites of microclones obtained by microdissection of a human chromosomal region 11q23 and isolation of yeast artificial chromosomes

Summary A human chromosomal region 11q23-specific DNA library has been constructed by means of microdissection-microcloning method with polymerase chain reaction (PCR) technique (Sekiet al., Genomics16: 1993). DNA sequences were determined for 25 microclones that contained approximately 300–500 bp insert and gave a unique (single copy) signal in Southern blot analysis. The sequence tagged site (STS) was designed and appropriate condition for PCR was determined for each unique microclone. Twelve STSs were established and used for PCR-screening of human genomic libraries constructed with yeast artificial chromosome (YAC). Thirteen YAC clones have been isolated from eight STSs. These chromosomal region-specific STSs and YAC clones will be useful in the positional cloning of disease-related genes localized to the q23 region of chromosome 11.     

Sensation and control of breathing: A dynamic model

A dynamic model of the CO₂ respiratory control system is proposed, which can provide a qualitative basis for predicting breathing sensations. The discomfort index, which represents breathing sensations, is assumed to be composed of two sources: the arterial CO₂ level and the respiratory motor command. The respiratory controller receives inhibitory neuromechanical and excitatory CO₂ signals from the plant. The CO₂ signal is enhanced by exercise stimuli. This dynamic multiplicative-type controller is used in simulations of key experiments: exercise and CO₂ rebreathing with and without resistive loading. The dynamics of the discomfor index, the respiratory motor command, ventilation, and arterial CO₂ concentration conform to the experimental data. The perceptual sensitivity to CO₂ relative to respiratory effort is significantly correlated with the slope of hypercapnic ventilatory response. This result shows a clear linkage between ventilatory response and breathing sensations. Although it is shown that the automatic controller effectively minimizes the discomfort index for perturbations about an operating point under certain conditions, the discomfort index itself does not seem to be an underlying control principle of the proposed automatic controller model. Rather, breathing sensations may influence ventilatory responses by modifying the output of the automatic controller.     

PRIMARY FIBROSARCOMA OF THE LIVER WITH HYPOGLYCEMIA

An autopsy case of primary hepatic fibrosarcoma with severe hypoglycemia is reported. Only two cases have been previously reported. Histological features were well differentiated and partly indistinguishable from those of fibrous mesothelioma.     

Retarded gastric acid secretion in rats infected with larval Taenia taeniaeformis

The influence of hepatic larval Taenia taeniaeformis infection on gastric acid secretory activity and gastric mucosal integrity was investigated. After 12 weeks of infection with 2,000 T. taeniaeformis eggs, the gastric pH values of control and infected rats were 4.1+/-0.6 (mean +/- SD) and 8.4+/-0.2, respectively. There was no difference in the basal acid secretion between control (1.7+/-0.7 micro Eq.H(+)/15 min) and infected (1.9+/-0.3) rats. However, infected rats failed to respond to histamine stimulation, the maximum acid output level being 2.8+/-0.4 in the infected rats, compared to 12.9+/-3.3 in control rats. Larval T. taeniaeformis infection resulted in the suppression of gastric acid secretion leading to hypergastrinemia.     

Heritable unstable DNA sequences and hypermethylation associated with fragile X syndrome in Japanese families

Fragile X syndrome, associated with the fragile site at Xq27.3 (FRAXA), is the most common form of familial mental retardation. The fragile X mutation has recently been characterized as a heritable unstable DNA sequence, p(CCG)n/p(CGG)n, in the FRAXA locus. In the present study, a correlation between fragile X-genotypes in the FRAXA locus and hypermethylation of an adjacent CpG island was examined in four Japanese families with fragile X syndrome. We show here that the heritable unstable DNA sequences in the fragile X chromosome usually increase in size when transmitted by female carriers, and that the degree of methylation in the CpG island correlated with the increased sizes of the unstable DNA sequences. When a hypermethylated full mutation was transmitted by a male to his daughters, both the size of the unstable DNA sequence and the degree of the methylation reduced to the premutation range. Our observations suggest that female meiosis has a greater potential for amplifying unstable DNA sequences and that amplified DNA sequences can be transmitted through germ cells, while male germ cells seem not to be able to tolerate highly amplified unstable DNA sequences.     

Implantable chemotherapy‐loaded silk protein materials for neuroblastoma treatment

Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multicycle chemotherapies, resulting in short‐ and long‐term toxicities. Here, we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment. The intratumoral drug concentration was significantly higher with intratumoral delivery versus IV. Furthermore, intratumor delivery decreased the maximum plasma concentration compared to IV delivery, reducing systemic exposure and possibly reduing long‐term side effects of chemotherapy exposure. Histopathologically, tumors with remission periods >25 days before recurrence transformed from a “small‐round‐blue cell” (SBRC) to predominantly “large cell” neuroblastoma (LCN) histopathology, a more aggressive tumor subtype with unfavorable clinical outcomes. These results show that intratumoral chemotherapy delivery may be a treatment strategy for pediatric neuroblastoma, potentially translatable to other focal tumors types. Furthermore, this treatment modality allows for a clinically relevant mouse model of tumor transformation that may be used for studying the phenotypical tumor recurrence and developing more effective treatment strategies for recurrent tumors.     

The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology

Respiratory activities are produced by medullary respiratory rhythm generators and are modulated from various sites in the lower brainstem, and which are then output as motor activities through premotor efferent networks in the brainstem and spinal cord. Over the past few decades, new knowledge has been accumulated on the anatomical and physiological mechanisms underlying the generation and regulation of respiratory rhythm. In this review, we focus on the recent findings and attempt to elucidate the anatomical and functional mechanisms underlying respiratory control in the lower brainstem and spinal cord.