This paper describes Data Modeling for unstructured data of Diffusion Tensor Imaging (DTI). Data Modeling is an
essential first step for data preparation in any data management and data mining procedure. Conventional Entity-
Relational (E-R) data modeling is lossy, irreproducible, and time-consuming especially when dealing with unstructured
image data associated with complex systems like the human brain. We propose a methodological framework for more
objective E-R data modeling with unlimited query support by eliminating the structured content-dependent metadata
associated with the unstructured data. The proposed method is applied to DTI data and a minimum system is
implemented accordingly. Eventually supported with navigation, data fusion, and feature extraction modules, the
proposed system provides a content-based support environment (C-BASE). Such an environment facilitates an unlimited
query support with a reproducible and efficient database schema. Switching between different modalities of data, while
confining the feature extractors within the object(s) of interest, we supply anatomically specific query results. The price
of such a scheme is relatively large storage and in some cases high computational cost. The data modeling and its
mathematical framework, behind the scene of query executions and the user interface of the system are presented in this
We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor
where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal
ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID
mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of
near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the
intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the
intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier.
Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average,
3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8±4.1ºC. Identical laser
doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of
48.6±1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of
nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of
treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.
Despite convincing evidence for hyperthermic radiosensitization, the invasive means of achieving and monitoring
hyperthermia and the lack of good thermal dosimetry have hindered its use in routine clinical practice. A non-invasive
method to generate and monitor hyperthermia would provide renewed enthusiasm for such treatments. Near-infrared
absorbing gold nanoshells have been shown to accumulate preferentially in tumors via the enhanced permeability and
retention effect and have been used for thermal ablation of tumors. We evaluated the use of these nanoshells to generate
hyperthermia to evaluate the anti-tumor effects of combining gold nanoshell mediated hyperthermia with radiotherapy.
Laser settings were optimized for hyperthermia in a mouse xenograft model to achieve a temperature rise of 40- 41°C in
the tumor periphery and 37-38°C (ΔT=4-5°C) deeper within the tumors. The ΔT measurements were verified using both
thermocouple and magnetic resonance thermal imaging (MRTI) temperature measurements. Tumor re-growth delay was
estimated by measuring tumor size after treatment with radiation (10Gy single dose), hyperthermia (15 minutes at 40°C),
and hyperthermia followed by radiation and control. Significant difference (p <0.05) in the tumor volume doubling time
was observed between the radiation group (13 days) and combination treatment group (25 days). The
immunofluorescence staining for the hypoxic, proliferating cells and the vasculature corroborated our hypothesis that the
radiosensitization is in part mediated by increased initial perfusion and subsequent collapse of vasculature that leads to
acute inflammatory response in the tumor. The increased vascular perfusion immediately after gold nanoshell mediated
hyperthermia is confirmed by dynamic contrast enhanced magnetic resonance imaging.
Cooled fiber tip technology has significantly improved the volume coverage of laser induced thermal therapy (LITT),
making LITT an attractive technology for the minimally invasive treatment of cancer. Gold coated nanoshells can be
tuned to experience a plasmon resonance at a desired laser frequency, there introduction into the treatment region can
greatly amplify the effectiveness of the thermal treatment. The goal is to conformaly heat the target, while sparing
surrounding healthy tissue. To this end a treatment option that is self-confining to the target lesion is highly desirable.
This can be achieved in the liver by allowing nanoshells to be taken up by the healthy tissue of the liver as part of their
natural removal from the blood stream. The lesion is then incased inside the nanoshell laden tissue of the surrounding
healthy tissue. When an interstitial laser probe is introduced into the center of the lesion the thermal radiation scatters
outward until it interacts with and is absorbed by the nanoshells located around the lesion periphery. As the periphery
heats it acts as secondary source of thermal radiation, sending heat back into lesion and giving rise to ablative
temperatures within the lesion while sparing the surrounding tissue.
In order to better monitor therapy and know when the target volume has been ablated, or exceeded, accurate knowledge
is needed of both the spatial distribution of heating and the maximum temperature achieved. Magnetic resonance
temperature imaging (MRTI) is capable of monitoring the spatiotemporal distribution of temperature in vivo.
Experiments have been performed in vitro using a dog liver containing nanoshells (concentration 860ppm) and a tissue
like lesion phantom designed to have the optical properties of liver metastasis .
Minimally invasive thermal therapy is gaining ground as a new treatment modality of prostate tumors. However, further
understanding of molecular events like HSP70 expression is required for treatment planning and coordination with
chemotherapy and radiation. Metastatic prostate tumor (PC3 MM2) cells, transduced with reporter genes, were utilized
to study the expression of HSP70 induced by normal and nanoshell-mediated heating. A correlation was noted between
HSP70 expression, cellular viability and heating temperatures. This imaging paradigm can be developed into a PET-MR
thermal treatment regimen, which would include dosimetry planning, real time temperature monitoring and post
treatment assessment of tumor response at a cellular level.
This study investigates the potential of using gold nanoshells to mediate a thermally induced modulation of tumor
vasculature in experimental prostate tumors. We demonstrate that after passive extravasation and retention of the
circulating nanoshells from the tumor vasculature into the tumor interstitium, the enhanced nanoshells absorption of
near-infrared irradiation over normal vasculature, can be used to increase tumor perfusion or shut it down at powers
which result in no observable affects on tissue without nanoshells. Temperature rise was monitored in real time using
magnetic resonance temperature imaging and registered with perfusion changes as extrapolated from MR dynamic
contrast enhanced (DCE) imaging results before and after each treatment. Results indicate that nanoshell mediated
heating can be used to improve perfusion and subsequently enhance drug delivery and radiation effects, or be used to
shut down perfusion to assist in thermal ablative therapy delivery.
Laser induced thermal therapy is used in conjunction with gold coated silica core nanoshells and magneticresonance
temperature imaging (MRTI). The nanoshells are embedded in phantom or in vivo tumors and
heat preferentially compared to surrounding tissue when the laser is applied. The tissues thermal response
is varied by either the laser power or the nanoshell concentration. In this way precise control of the heating
can be achieved. This results in the ability to quantitatively monitor therapeutic temperature changes that
occur in a spatiotemporally controlled way. This provides an unprecedented means proscribing and
monitoring a treatment in real time and the ability to make precise corrections when necessary.