Phantom Tumor Research Articles

Semi-automated Image Processing for Preclinical Bioluminescent Imaging.

Bioluminescent imaging is a valuable noninvasive technique for investigating tumor dynamics and specific biological molecular events in living animals to better understand the effects of human disease in animal models. The purpose of this study was to develop and test a strategy behind automated methods for bioluminescence image processing from the data acquisition to obtaining 3D images. In order to optimize this procedure a semi-automated image processing approach with multi-modality image handling environment was developed. To identify a bioluminescent source location and strength we used the light flux detected on the surface of the imaged object by CCD cameras. For phantom calibration tests and object surface reconstruction we used MLEM algorithm. For internal bioluminescent sources we used the diffusion approximation with balancing the internal and external intensities on the boundary of the media and then determined an initial order approximation for the photon fluence we subsequently applied a novel iterative deconvolution method to obtain the final reconstruction result. We find that the reconstruction techniques successfully used the depth-dependent light transport approach and semi-automated image processing to provide a realistic 3D model of the lung tumor. Our image processing software can optimize and decrease the time of the volumetric imaging and quantitative assessment. The data obtained from light phantom and lung mouse tumor images demonstrate the utility of the image reconstruction algorithms and semi-automated approach for bioluminescent image processing procedure. We suggest that the developed image processing approach can be applied to preclinical imaging studies: characteristics of tumor growth, identify metastases, and potentially determine the effectiveness of cancer treatment.

A hybrid imaging method based on diffuse optical tomography and optomechanical method to detect a tumor in the biological phantom

In this study, a new combined method to detect abnormality inside the biological phantom is presented. We describe a new approach to breast imaging based on diffuse optical tomography and optomechanical imaging. In this method, the diffusion of photons inside compressed breast phantom is used to detect the location of abnormalities. The variation of optical properties of phantom induced by compression can affect on diffusion of photons. Therefore, these variations of optical properties of phantom must be considered in this imaging method. In current study, the ability of this method to detect the location of tumor inside biological phantom is evaluated. The results show that the accuracy of this method is better than diffuse optical tomography.

The PSTD Method with the 4th-Order Time Integration for 3D TAT Reconstruction of a Breast Model

The thermoacoustic tomography (TAT) is a novel noninvasive and nonionizing medical imaging modality for breast cancer detection. In the TAT, a short pulse of microwave is irradiated to the breast tissue. The tissue absorbs the microwave energy and is heated up momentarily, thus it generates acoustic waves due to the thermoelastic expansion. If the pulse width of the microwave radiation is around one microsecond, the generated acoustic waves are ultrasonic and are in the MHz range. Wide-band ultrasonic transducers are employed to acquire the time-resolved ultrasound signals, which carry information about the microwave absorption properties (mainly related to conductivities) of different tissues. An image showing such properties can then be reconstructed from the time-resolved ultrasound signals. Most existing TAT reconstruction methods are based on the assumption that the tissue under study is acoustically homogeneous. In practice, however, most biological tissues are inhomogeneous. For example, the speed of sound has about 10% variation in breast tissue. The acoustic heterogeneity will cause phase distortion of the pressure field, which will in turn cause blurring in the reconstructed image, thus limiting the ability to resolve small objects. In this work, a 3D inhomogeneous reconstruction method based on pseudo-spectral time-domain (PSTD) is presented to overcome this problem. The method includes two steps. The first step is a homogeneous reconstruction process, from which an initial image is obtained. Since the inhomogeneity itself is usually an acoustic source, the shape and location of the inhomogeneity can be estimated. Then, the acoustic properties of the inhomogeneities (available from the literatures for known tissue types) are assigned to the classified regions, and the other reconstruction based on the updated acoustic property map is conducted. With this process, the phase distortion can be effectively corrected. So it can improve the ability to image small objects. A 3D breast phantom is used to study the proposed method. The breast phantom was generated based on the data set of the Visible Human Project. Regions of different tissue types have been classified and acoustic and electric properties are assigned to such regions. Small phantom tumors placed in the breast phantom have been reconstructed successfully with the inhomogeneous reconstruction method. Improved resolution has been achieved compared to that obtained by homogeneous method.

Data acquisition system for harmonic motion microwave Doppler imaging.

Harmonic Motion Microwave Doppler Imaging (HMMDI) is a hybrid method proposed for breast tumor detection, which images the coupled dielectric and elastic properties of the tissue. In this paper, the performance of a data acquisition system for HMMDI method is evaluated on breast phantom materials. A breast fat phantom including fibro-glandular and tumor phantom regions is produced. The phantom is excited using a focused ultrasound probe and a microwave transmitter. The received microwave signal level is measured on three different points inside the phantom (fat, fibro-glandular, and tumor regions). The experimental results using the designed homodyne receiver proved the effectiveness of the proposed setup. In tumor phantom region, the signal level decreased about 3 dB compared to the signal level obtained from the fibro-glandular phantom area, whereas this signal was about 4 dB higher than the received signal from the fat phantom.

A Telerobotic System for Transnasal Surgery.

Mechanics-based models of concentric tube continuum robots have recently achieved a level of sophistication that makes it possible to begin to apply these robots to a variety of real-world clinical scenarios. Endonasal skull base surgery is one such application, where their small diameter and tentacle like dexterity are particularly advantageous. In this paper we provide the medical motivation for an endonasal surgical robot featuring concentric tube manipulators, and describe our model-based design and teleoperation methods, as well as a complete system incorporating image-guidance. Experimental demonstrations using a laparoscopic training task, a cadaver reachability study, and a phantom tumor resection experiment illustrate that both novice and expert users can effectively teleoperate the system, and that skull base surgeons can use the robot to achieve their objectives in a realistic surgical scenario.

Feasibility of electric property tomography of pelvic tumors at 3T.

Investigation of the validity of the "transceive phase assumption" for Electric Property Tomography of pelvic tumors at 3T. The acquired electric conductivities of pelvic tumors are beneficial for improved specific absorption rate determination in hyperthermia treatment planning. Electromagnetic simulations and magnetic resonance imaging measurements of a pelvic-sized phantom and the human pelvis of a volunteer and a cervix cancer patient. The reconstructed conductivity values of the phantom tumor model are in good quantitative agreement (mean deviation: 1-10%) with the probe measurements. Furthermore, the average reconstructed conductivity of a pelvic tumor model was in close agreement with the input conductivity (0.86 S/m vs. 0.90 S/m). The reconstructed tumor conductivity of the presented patient (cervical carcinoma, Stage: IVA) was 1.16 ± 0.40 S/m. This study demonstrates the feasibility of electric property tomography to measure quantitatively the conductivity of centrally located tumors in a pelvic-sized phantom and human pelvis with a standard magnetic resonance (MR) system and MR sequences. A good quantitative agreement was found between the reconstructed σ-values and probe measurements for a wide range of σ-values and for off-axis located spherical compartment. As most pelvic tumors are located in the central region of the pelvis, these results can be exploited in hyperthermia treatment planning systems.

High-frequency ultrasonic measurement of vascularization in phantoms and Avastin-treated mice with breast tumors

Tissue vascularization is an important aspect of tissue engineering and oncology. The objective of this study was to determine if direct ultrasonic measurements in the 10–100 MHz range could be used as an in vivo vascularization assay. To simulate vascularization of tissue, phantoms were fabricated from agarose gel inclusions embedded in a gelatin-soluble fiber mixture. Ultrasonic tests were performed using two broadband ultrasonic transducers centered at 50 MHz. Results showed the samples with multiple agarose vasculature structures decreased the ultrasound wavespeed. As the level of vasculature decreased, the wavespeed of the ultrasound increased. Further investigation of vascularization included the in vivo evaluation of grafted breast cancer tumors in mice. The experimental group was composed of mice treated with Avastin, an angiogenesis inhibitor. The heterogeneity of the vasculature in the control tissue resulted in the scattering of the ultrasound, decreasing the wavespeed. Because the treated group contained less vascularized, more homogeneous tissue, the wavespeed was significantly higher. Results from both the phantom and mouse tumor studies revealed that the ultrasound wavespeed was inversely proportional to the level of vasculature. The results indicate that direct ultrasound wavespeed measurements in the 10–100 MHz range can be used to identify vascularization in tissue.

Phantom tumor of the lung in a patient with preserved left ventricular systolic function

A 69-year-old male patient chronic smoker with a past history of hypertension, myocardial infarction was admitted with complaints orthopnea. Examina­tion revealed a blood pressure of 150/100 mmHg, pulse 114/min, tachypnea, jugular venous disten­tion. Extensive bilateral crackles over both lung fields. The findings were consistent with the diagno­sis of acute pulmonary edema. Chest radiography and tomography revealed a spherical mass in the middle lobe of the right lung, obscuring the right side of the cardiac silhouette (Fig. 1). Echocardiographic evaluation showed preserved left ventricular systol­ic function with ejection fraction of 60%, and signs of restrictive type of diastolic dysfunction (E/A=4.8, DT 100 msec). An increase in diuretic dose result­ed in improvement in the patient’s symptoms and A repeat radiograph and tomography (Fig. 2) after successful treatment of the acute pulmonary edema showed complete resolution of the opacity consis­tent with the diagnosis of “pseudotumor” or “vanish­ing tumor” or “phantom tumor” of the lung. Phantom tumor is generally believed to occur in patients with systolic dysfunction (1). Phantom tumor of the lung refers to the accumulation of fluid in the interlobar spaces as a result of congestive heart failure, giving the radiological appearance of a neoplasm. Rapid radiological improvement in response to treatment for heart failure is a classical feature of this clini­cal entity. Although phantom tumor is generally be­lieved to occur in patients with systolic dysfunctio, in our case, its appearance was secondary to diastolic dysfunction. We presented phantom tumor of the lung in a patient with preserved left ventricular sys­tolic function.

Rapidly vanishing lung pseudotumor in a patient with acute bilateral bronchopneumonia

Rapidly vanishing lung pseudotumor (phantom tumor) refers to the transient well-demarcated accumulation of pleural fluid in the interlobar pulmonary fissures. Most frequently their appearance is associated with congestive heart failure, but also other disorders like hypoalbuminemia, renal insufficiency or pleuritis. Its rapid disappearance in response to the treatment of the underlying disorder is a classical feature of this clinical entity. A 47-year-old woman, chronic smoker with symptoms of shortness of breath, orthopnea, chills, cough, weakness and the temperature of 39.2 degrees C was admitted to our hospital. A posteroanterior chest X-ray revealed cardiomegaly with the cardiothoracic ratio of > 0.5, blunting of both costophrenic angles and an adjacent 6 x 5 cm well-defined, rounded opacity in the right interlobar fissure. Transthoracic 2-dimensional echocardiography demonstrated left ventricular hyperthrophy with a systolic ejection fraction of 25% and moderate mitral regurgitation. The patient's symptoms resolved rapidly after diuresis, and repeated chest X-ray four days later showed that the right lung opacity and pleural effusions had vanished. The presented case underlines the importance of the possibility of vanishing lung tumor in patients with left ventricular failure and a sharp oval lung mass on the chest X-ray. This is the way to avoid incorrect interpretation of this finding causing additional, unnecessary, costly or invasive imaging, interventions and drugs.

Phantom tumour of the lung

A 79-year-old man presented with an 8 h history of shortness of breath and oedematous legs. He had a history of hypertension, atrial fi brillation, and chronic obstructive pulmonary lung disease. He was on long term ipratropium bromide, irbesartan, amlodipine, amioda rone, and furosemide. He had normal vital signs and the only relevant fi ndings in physical examination were bilateral oedema of both legs and rales in the lower half of both lungs. Radiograph of the chest showed an opaque elliptic image (red arrow) in the horizontal fi ssure and a round tumour-like image in the right inferior lobe (green arrow) (fi gure A). Our patient was treated with furosemide with clinical improvement. A second radiograph of the chest

Primary adenocarcinoma of the seminal vesicles: a phantom tumor

Primary adenocarcinoma of the seminal vesicles: a phantom tumor

Primary adenocarcinoma of the seminal vesicles - a phantom tumour

Primary adenocarcinoma of the seminal vesicles (ASV) is a very rare neoplasm with less than 50 histologically confirmed cases reported in the literature. The diagnosis is generally difficult and is based on a combination of morphologic, immunohistochemical, and clinical findings, including radiologic examination. It is difficult to make a definitive diagnosis using biopsy, and surgical resection is usually required to determine whether or not the tumour is primary to the seminal vesicles. We present a case of primary ASV found upon investigation of inguinal lymphadenopathy. A history of recent hormonal manipulations for the treatment of infertility may be associated with the development or the progression of this rare tumour.

Phantom tumour of the lung

Phantom tumour of the lung

SU-E-T-493: 4D Considerations for Active-Scanning Proton Beams

Purpose: To optimize delivery parameters for mobile targets treated with active-scanning proton beams. Methods: An algorithm was developed to sort delivery of scanned proton plans into temporal bins. The binning reflects various dose rates and respiratory periods. A single-field proton plan was generated to treat a target within a phantom. The delivery of the plan was sorted into temporal bins, and the bins were displaced spatially to simulate residual motion within a respiratory gated delivery. The binned delivery was repeated multiple times with random starting points. Weighted combinations of the varied start points were formed to simulate repainting as a means of neutralizing intra-gate motion. This process was extended to a plan generated for a single phase of a 4DCT scan of a lung tumor. Intra-gate motion was simulated by binning the delivery and calculating portions on neighboring 4DCT phases. The dose matrices were deformably remapped back onto the planned 4DCT phase and the matrices were summed to yield the delivered dose. As with the phantom plan, various ranges of motion and repainting were simulated.Results: Simulated motion of a phantom tumor volume yields shallower DVH fall off than a static displacement of the same magnitude, although both hot and cold spots are observed. Simulated repaintings of the volume mitigated coverage inhomogeneities. Because of lower density tissue surrounding the lung tumor, simulated intra-gate motion results in a reduction of dose to the tumor. Conclusions: By varying the range of simulated motion and number of repaintings we will optimize duty cycle and delivery parameters for scanning proton treatment of a mobile tumor. J Kruse is supported in part by a grant from Varian Medical Systems, Inc.

Miniature kilohertz-frequency ultrasound implant for brain drug delivery.

Glioblastoma multiforme is a highly aggressive brain malignancy currently treated by surgical resection, radiotherapy, and local drug delivery. However, due to heterogeneities in neural tissue and tumor cell migration into surrounding healthy tissue, treatment strategies remain ineffective and patient prognosis poor. We have shown that low intensity focused and nonfocused ultrasound may safely enhance the penetration and distribution of chemotherapeutics delivered locally via convection-enhanced infusions in rodent brain parenchyma in vivo. In scaling the ultrasound-assisted therapy from rodent to large animal and increasing its clinical translatability, we designed a miniature kilohertz (100 and 600 kHz) ultrasound implant that can be placed within the brain tumor resection cavity during patient recovery to assist chemotherapy. The miniature ultrasound system has been tested in a diffusion-based human-sized agarose brain phantom tumor model under various acoustic intensities and pulse sequences. Results indicate that ultrasound increases the volume of tracer distribution by a factor of 2–3 compared with controls. We present the effects of acoustic intensity and pulse interval from the implant on distribution of tracers in vitro and ex vivo in the phantom model and intact equine brain, respectively. The miniature ultrasound implant provides significant drug distribution gains that may improve patient outcome.

Comparison of Semiautomated and Manual Measurements for Simulated Hypo- and Hyper-attenuating Hepatic Tumors on MDCT: Effect of Slice Thickness and Reconstruction Increment on Their Accuracy

The aims of this study were to compare accuracy between semiautomated and manual measurements of the longest diameter and volume of simulated hepatic tumors in phantoms and to evaluate the effects of slice thickness (ST) and reconstruction increment (RI) on accuracy. Liver phantoms with 45 hypoattenuating and 45 hyperattenuating lesions of different sizes (diameter, 13.3-50.7 mm; volume, 0.4-54.0 mm(3)) and shapes (spherical or elliptical) were scanned using a 64-row multidetector computed tomographic scanner. Images were reconstructed with ST and RI settings of 0.75 and 0.7 mm, 1.0 and 0.7 mm, 1.5 and 1.0 mm, 3.0 and 2.0 mm, 3.0 and 3.0 mm, and 5.0 and 5.0 mm. The longest diameter and volume of each lesion were measured both manually and semiautomatically. To assess accuracy, measurements were compared to reference values by calculating absolute percentage error. Comparisons of absolute percentage error between methods and between ST and RI settings were performed using paired t tests. The degree of correlation between each measurement and a reference value was also assessed. The semiautomated method showed significantly higher accuracy than the manual method in volume for most ST and RI settings (0.75 and 0.7 mm, 1.0 and 0.7 mm, and 1.5 and 1.0 mm in hypoattenuating lesions and all settings in hyperattenuating lesions; P < .05) and showed similar accuracy in diameter for all ST and RI settings regardless of lesion attenuation (P > .05). Semiautomated measurements also demonstrated higher correlation with reference values than the manual method for both diameter and volume. The absolute percentage error tended to be increased as ST and RI increased for both methods, and acceptable maximum ST and RI in semiautomated method were 1.5 and 1.0 mm. Semiautomated computed tomographic measurement showed higher accuracy and correlation than the manual method in measuring the diameter and volume of hepatic lesions. The accuracy of both methods was highly dependent on z-axis resolution.

Poster - Thur Eve - 71: Evaluation of a Breathing Phantom's Tumour Motion Using Portal Images and an Optical Flow Tracking Algorithm

Purpose: The efficacy of external beam radiotherapy depends on the accuracy of radiationdose being delivered to the tumor while minimizing dose to surrounding tissues. In order to improve outcome, it is essential to have a real‐time method to track the motion of the tumor and surrounding critical organs.Methods: This paper presents the development, performance and feasibility of using an optical flow algorithm to track the motion of a tumor using Electronic Portal Images (EPI). The algorithm calculates optical flow vectors (u,v) associated with temporal changes of the image intensities in each pixel. Both single and multi‐resolution algorithms were developed and their performance evaluated using two methods. The first method uses a simulated image translation and the second uses an actual imagesequence of a moving lung tumor in an anthropomorphic phantom (RSD RS‐1500). Results: For a simulated 7‐pixel image translation, optical flow detects a corresponding 7‐pixel shift. For the actual imagesequence, a maximum velocity of 14 mm/s and 24 mm/s is detected with the single‐ and multi‐resolution algorithm respectively. This corresponds to a 61% and 33% difference compared to the measured maximum velocity.Conclusions: This study has demonstrated the potential of using an optical flow algorithm to track tumor and critical structure motion. In this novel attempt to compare the optical flow and measuredvelocities on EPI, it has been shown that further refinements including a modified actuator, increased EPI frame rate, and increased layers of the multi‐resolution algorithm are required to improve the tracking accuracy.

Dynamic spectral-domain optical coherence elastography for tissue characterization

A dynamic spectral-domain optical coherence elastography (OCE) imaging technique is reported. In this technique, audio-frequency compressive vibrations are generated by a piezoelectric stack as external excitation, and strain rates in the sample are calculated and mapped quantitatively using phase-sensitive spectral-domain optical coherence tomography. At different driving frequencies, this technique provides contrast between sample regions with different mechanical properties, and thus is used to mechanically characterize tissue. We present images of a three-layer silicone tissue phantom and rat tumor tissue ex vivo, based on quantitative strain rate. Both acquisition speed and processing speed are improved dramatically compared with previous OCE imaging techniques. With high resolution, high acquisition speed, and the ability to characterize the mechanical properties of tissue, this OCE technique has potential use in non-destructive volumetric imaging and clinical applications.

Contrast-enhanced microwave imaging of breast tumors: a computational study using 3D realistic numerical phantoms

The detection of early-stage tumors in the breast by microwave imaging is challenged by both the moderate endogenous dielectric contrast between healthy and malignant glandular tissues and the spatial resolution available from illumination at microwave frequencies. The high endogenous dielectric contrast between adipose and fibroglandular tissue structures increases the difficulty of tumor detection due to the high dynamic range of the contrast function to be imaged and the low level of signal scattered from a tumor relative to the clutter scattered by normal tissue structures. Microwave inverse scattering techniques, used to estimate the complete spatial profile of the dielectric properties within the breast, have the potential to reconstruct both normal and cancerous tissue structures. However, the ill-posedness of the associated inverse problem often limits the frequency of microwave illumination to the UHF band within which early-stage cancers have sub-wavelength dimensions. In this computational study, we examine the reconstruction of small, compact tumors in three-dimensional numerical breast phantoms by a multiple-frequency inverse scattering solution. Computer models are also employed to investigate the use of exogenous contrast agents for enhancing tumor detection. Simulated array measurements are acquired before and after the introduction of the assumed contrast effects for two specific agents currently under consideration for breast imaging: microbubbles and carbon nanotubes. Differential images of the applied contrast demonstrate the potential of the approach for detecting the preferential uptake of contrast agents by malignant tissues.

SU‐GG‐T‐289: A Lifelike Breathing Phantom and Model Tumor for IGRT and 4D Dose Calculation Applications

Purpose: To evaluate an anatomical breathing phantom and model lung tumor for IGRT and 4D applications. Method and Materials: The shape of a tumor was extracted from a patient's CT image, and a replica tumor created in a flexible resin using rapid‐prototyping techniques. A 5mm grid of fine holes was included in the model tumor to allow insertion of up to 30 micro‐mosfets. The physical characteristics of this tumor were compared with those of real patient tumors. This tumor was inserted into a commercial anatomic breathing phantom (RSD Inc.). This phantom includes spine, and a flexible ribcage. The tumor and phantom's chest motion were programmed using real patient traces. CT images (4D and free breathing), kilo‐voltage setup images (including fluoroscopy), and mega‐voltage portal images were compared with those from real patients. Twenty mosfets were inserted into the model tumor, and the phantom was irradiated using a step‐and‐shoot IMRT plan. The expected dose distribution was calculated using a previously validated 4D Monte Carlo technique. Results: The appearance of the phantom/tumor in kV and MV images was very similar to real patient images. The average CT number of the model tumor was 76 (at 120kVp), compared with 30 for the real patient (an effective difference in electron density of 2%). Its physical density and hardness was 1.3g cm−3 and 27durometers (range for real tumors: 0–60), respectively. The CT numbers of the bone and soft tissue regions of the breathing phantom were in the range found for real patients. The CT number of the lung material was the same as air. Agreement between the 4D Monte Carlo and experimental DVH was better than 3%. Conclusion: Rapidprototyping techniques can be used to produce realistic low cost model tumors that, in combination with an anatomical breathing phantom, can be used for IGRT and 4D applications.