Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.
Drug Delivery Systems ; Genetic Therapy ; Microbubbles ; Ultrasonography

BACKGROUND: Malignant lymphomas are classified on the basis of morphology, immunohistochemistry, and genetic and molecular biological features. Morphology is considered the most important and basic feature. Lymphomas can be classified as small, medium, or large depending on the cell size, but this criterion tends to be rather subjective. The aim of this study was to investigate the usefulness of an objective approach based on quantitative measurements. METHODS: Twenty specimens of mantle cell lymphoma and 2 specimens of the tonsil were examined. The nuclear area of 6,401 tumor cells of mantle cell lymphoma and 743 normal mantle cells of reactive tonsils were measured by 3 authors by using a user-controlled image-analyzer. The images of the nuclei were outlined using the spline method and the i-solution software, and the data were assessed using ANOVA and Student's t-test. RESULTS: The mean nuclear areas of mantle cell lymphoma cells measured by the 3 authors were 37.9 [7.9] microm2, 37.9 [7.2] microm2, and 38.2 [7.7] microm2 and those of normal mantle cells in reactive tonsil were 28.6 [2.3] microm2, 28.8 [2.0] microm2, and 27.0 [3.0] microm2. There was no statistical difference between the 3 observations of mantle cell lymphoma (P=0.580) and normal tonsils. CONCLUSION: For morphology, nuclear area is considered an important feature in the classification schemes of lymphoma. We showed that nuclear area measurement by using image analyzer can be used as an objective quantitative method. We think that nuclear morphometry may play a significant role in the diagnosis of lymphoma.
Cell Size ; Immunohistochemistry ; Lymphoma ; Lymphoma, Mantle-Cell ; Palatine Tonsil

This report describes an uncommon and fatal case of myocardial infarction due to coronary embolus arising from vegetation in the aortic valve with a background of infective endocarditis (IE). There are various causes of fatal IE. Myocardial infarction due to septic emboli is rare. We report a case of sudden death in a 69-year-old woman with hyperlipidemia and no known cardiac disease. She had severe general weakness and was hospitalized for colonoscopy. The patient unexpectedly presented with cardiac arrest and died. The autopsy showed total occlusion of the left anterior descending artery by an embolus, which originated from the septic vegetation of the aortic valve. Myocardial infarction from septic emboli associated with IE can be fatal and manifested as the first presentation. In autopsy practice of deceased patients with IE, careful examination of the coronary arteries is required.

Purpose: To develop a 3D magnetic resonance fingerprinting (MRF) method for application in high resolution knee cartilage PD, T1 , T2 mapping. Materials and Methods: A novel 3D acquisition trajectory with golden-angle rotating radial in kxy direction and interleaved echo planar imaging (EPI) acquisition in the kz direction was implemented in the MRF framework. A centric order was applied to the interleaved EPI acquisition to reduce Nyquist ghosting artifact due to field inhomogeneity. For the reconstruction, singular value decomposition (SVD) compression method was used to accelerate reconstruction time and conjugate gradient sensitivity-encoding (CG-SENSE) was performed to overcome low SNR of the high resolution data. Phantom experiments were performed to verify the proposed method. In vivo experiments were performed on 6 healthy volunteers and 2 early osteoarthritis (OA) patients. Results: In the phantom experiments, the T1 and T2 values of the proposed method were in good agreement with the spin-echo references. The results from the in vivo scans showed high quality proton density (PD), T1 , T2 map with EPI echo train length (NETL = 4), acceleration factor in through plane (Rz = 5), and number of radial spokes (Nspk = 4). In patients, high T2 values (50-60 ms) were seen in all transverse, sagittal, and coronal views and the damaged cartilage regions were in agreement with the hyper-intensity regions shown on conventional turbo spin-echo (TSE) images. Conclusion The proposed 3D MRF method can acquire high resolution (0.5 mm3 ) quantitative maps in practical scan time (~ 7 min and 10 sec) with full coverage of the knee (FOV: 160 × 160 × 120 mm3 ).

Purpose: To develop a 3D magnetic resonance fingerprinting (MRF) method for application in high resolution knee cartilage PD, T1 , T2 mapping. Materials and Methods: A novel 3D acquisition trajectory with golden-angle rotating radial in kxy direction and interleaved echo planar imaging (EPI) acquisition in the kz direction was implemented in the MRF framework. A centric order was applied to the interleaved EPI acquisition to reduce Nyquist ghosting artifact due to field inhomogeneity. For the reconstruction, singular value decomposition (SVD) compression method was used to accelerate reconstruction time and conjugate gradient sensitivity-encoding (CG-SENSE) was performed to overcome low SNR of the high resolution data. Phantom experiments were performed to verify the proposed method. In vivo experiments were performed on 6 healthy volunteers and 2 early osteoarthritis (OA) patients. Results: In the phantom experiments, the T1 and T2 values of the proposed method were in good agreement with the spin-echo references. The results from the in vivo scans showed high quality proton density (PD), T1 , T2 map with EPI echo train length (NETL = 4), acceleration factor in through plane (Rz = 5), and number of radial spokes (Nspk = 4). In patients, high T2 values (50-60 ms) were seen in all transverse, sagittal, and coronal views and the damaged cartilage regions were in agreement with the hyper-intensity regions shown on conventional turbo spin-echo (TSE) images. Conclusion The proposed 3D MRF method can acquire high resolution (0.5 mm3 ) quantitative maps in practical scan time (~ 7 min and 10 sec) with full coverage of the knee (FOV: 160 × 160 × 120 mm3 ).

PURPOSE: To evaluate the clinical findings of diabetic patients with bilateral anterior ischemic optic neuropathy. METHODS: Three diabetic patients with bilateral anterior ischemic optic neuropathy showed different clinical findings. One eye developed AION and the contralateral eye was diagnosed with diabetic papilloapthy with a subclinical disc swelling in Case I. The contralateral eye with diabetic papillopathy progressed to AION 3 months after showing the initial symptoms. In Case II, one eye developed AION, which continued in the contralateral eye after 6 months. In Case III, AION developed in both eyes simultaneously. RESULTS: A fundus examination revealed an edema of the optic disc in all cases. Prominent leakage of fluorescein dye from the capillaries of the optic disc was demonstrated on fluorescein angiography. Different field patterns including central scotoma, paracentral scotoma, an enlarged physiologic blind spot, and the constriction of the peripheral field of the visual field were revealed on Goldmann perimetry. The visual evoked cortical potential showed decreased amplitude and a prolonged latency. The visual acuity of the five eyes improved after administering high dose methylprednisolone. However, visual acuity of one eye with diabetic papillopathy did not improve. CONCLUSIONS: The clinical findings of the anterior ischemic optic neuropathies in the diabetic patients vary, and their prognosis is fair in most cases.
Capillaries ; Constriction ; Edema ; Fluorescein ; Fluorescein Angiography ; Humans ; Methylprednisolone ; Optic Disk ; Optic Neuropathy, Ischemic* ; Prognosis ; Scotoma ; Visual Acuity ; Visual Field Tests ; Visual Fields

BACKGROUND: There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images. METHODS: We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells and captured typical microscopic findings. Using an image analyzer, we determined the longest nuclear line profiles and obtained graph files and Excel data on RGB light intensities. We assessed the meaningful differences in graph files and Excel data among the three different tumors. RESULTS: The nucleus of hematoxylin and eosin-stained tumor cells was expressed as a combination of RGB light sources. The highest intensity was from blue, whereas the lowest intensity was from green. According to the graph files, green showed the most noticeable change in the light intensity, which is consistent with the difference in standard deviations. CONCLUSIONS: The change in the light intensity for green has an important implication for differentiating between tumors. Specific features of the nucleus can be expressed in specific values of RGB light intensities.
Chromatin ; Hematoxylin ; Image Processing, Computer-Assisted ; Light ; Lung ; Neuroendocrine Tumors ; Rectum ; Small Cell Lung Carcinoma

Ehlers-Danlos syndrome type IV (EDS IV) is a hereditary disorder of the connective tissue, characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations of the gene for type III procollagen (COL3A1), resulting in insufficient collagen production or a defect in the structure of collagen. EDS IV can have fatal complications such as the rupture of great vessels or organs, which can cause hemorrhaging and sudden unexpected death. Here, we report a case of a 43-year-old female who collapsed after a struggle with a neighbor. In this patient, the bifurcation of the bilateral common iliac artery ruptured, with no evidence of trauma, inflammation, or atherosclerosis. Genetic analysis of COL3A1 showed the presence of a c.2771G>A (p.Gly924Arg) mutation, which may be associated with EDS IV. The forensic pathologist should consider the possibility that the spontaneous visceral or arterial rupture was caused by EDS IV. Genetic analysis is not currently a routine procedure during autopsy. However, in this case, we suggest that the patient possibly had an underlying EDS IV condition, and we recommended family members of the deceased to seek genetic analysis and counseling.
Adult ; Aortic Rupture* ; Arteries ; Atherosclerosis ; Autopsy ; Collagen ; Collagen Type III ; Connective Tissue ; Counseling ; Ehlers-Danlos Syndrome* ; Female ; Humans ; Iliac Artery ; Inflammation ; Rupture ; Rupture, Spontaneous ; Skin ; Uterus ; Veins

Recently, some cases of basal cell carcinoma (BCC) with lung metastasis have been reported, but those involving simultaneous tracheal, bronchial, and lung metastases have been rarely reported. Here, we have reported a very unusual case of BCC with metastasis, presenting with lung nodules and endobronchial lesions after two metastasectomies. Since BCC is a slow-growing cancer that rarely metastasizes to distant organs, tumor stage workup including radiological imaging has not been routinely performed in clinical practice. This case showed that BCC can metastasize to the lung, although the currently reported metastasis rate of BCC is extremely low.

Systemic lupus erythematosus (SLE) may occur in any organ. In patients with SLE, myocarditis is extremely rare and potentially life-threatening. Herein, we report on a patient with lupus myocarditis, diagnosed by myocardial biopsy, immunologic tests, and clinical manifestations. Our findings suggest that securing time for diagnosis via extracorporeal membrane oxygenation and other intensive care is helpful for obtaining a good prognosis.