Quantification of spatial expansion of cervical tumours using Magnetic Resonance Imaging

(艾提拉什)，(张兰)，(王培军)

Department of Radiology，Tongji Hospital of Tongji University，Shanghai 200065，China

Quantification of spatial expansion of cervical tumours using Magnetic Resonance Imaging

Ateelesh(艾提拉什)，Zhang Lan(张兰)，Wang Peijun(王培军)

Department of Radiology，Tongji Hospital of Tongji University，Shanghai200065，China

ObjectiveThis research study aims to analyze existing principles regarding the processing and analysis of imaging data and apply these concepts to the setting of the magnetic resonance imaging arena with a main focus on its use in cervical tumours.Any possible models will then be formulated，with the possibility of testing these theories in an experimental study that would involve actual patient data collected from a collaborating healthcare institution.The applicability of quantification of spatial expansion will also be applied to specific cancers and medical conditions that commonly make use of the non-invasive feature of magnetic resonance imaging.ConclusionDiffusion-weighted magnetic resonance imaging can be employed in examining the cellular dynamics of tumours as it assists in the localization，as well as displacement of particular cellular structures within a particular volume.

magnetic resonance imaging;cervical tumours

1 Introduction

Methodsin quantifying the extent of spatial expansion of cancer cells play a critical role in the improvement of monitoring schemes for the progression of cancer［1］.With the development of biochemical techniques in determining cellular responses to external stimuli such as drugs，heat and growth factors，the technology of visualizing cellular responses in terms of tumour size may serve as an essential instrument in the design of medical procedures that could eventually be applied in the hospital setting.

2 Quantification of spatial expansion of tumours

In the last decade，there has been a significant increase in the employment of non-invasive radiological techniques in the imaging of various body parts for the diagnosis of specific medical conditions.To date，most large hospitals around the world have acquired the equipment that allows magnetic resonance imaging(MRI)，as well as positron emission tomography(PET)and computerized tomography(CT)scanning of patients who are classified as possible candidates of particular internal medical disorders.Aside from ease in imaging specific organs or tissues for examination，there has also been a need to determine the status of the disease，in terms of the extent of necrosis or the size of a tumor.The improvement in theories in physics，such as the establishment of computational ways in determining signal intensity ratios and the calculation of volume and depth of images，has resulted in the generation of 3-dimensional images that are highly beneficial to biomedical professionals［2］.The advent of development of new techniques in cellular and molecular biology has also further improved the capacity of imaging techniques in visualizing organs，as these exist in vivo［3］.Using synthesized dyes that are relatively safe for patient administration，it is now possible to determine the rate of blood flow through specific blood vessels in the body［4］.The extent of permeability of cells according to the nature of a reagent can al-so be visualized using live-cell imaging，thus allowing researchers to monitor cellular uptake of a specific drug.The polarity of cells，in relation to the whole architecture of a tissue can now also be determined through the use of region-specific dyes that hybridize to specific moieties of macromolecules［5］.It is also possible to determine the rate of biochemical processes within tissues，such as those in response to hypoxia and other oxidation-reduction pathways［6］.A number of clinical trials are now in progress，with the possibility of getting an approval from food and drug authorities to market these products for hospital use during medical diagnostic procedures.

One of the main challenges in the field of radiology and oncology is the determination of changes in the size of a tumour in a patient［7］.The classical methods of x-ray，ultrasonography，mammography and MRI have provided useful information on the approximate size of a tumor in a specific organ.However，changes in tumour size need to be monitored on a regular basis，in order to determine the degree of proliferation and aggressiveness of the cancer.More importantly，tissue texture and composition are also additional，yet critical information that need to be established in the diagnosis of cancer.There are certain adhesion molecules that are present on the surface of cancer cells，assisting in the migration of these cells to other regions of the body.

3 Magnetic resonance imaging of cervical tumours

Magnetic resonance imaging is currently regarded as the most accurate technology in imaging，as well as staging cancers of the female reproductive system，including endometrial and cervical cancer［8，1］.This noninvasive technique allows the measurement of the extent of myometrial infiltration，which plays an essential role in the establishment of the prognosis of the condition of a patient.The technique also employs infiltration information on planning the appropriate therapeutic regimen that should be conducted on the patient.The recent development of faster sequences using gadolinium-DTPA contrast media has significantly improved the precision of magnetic resonance imaging in the diagnosis of cancer.It has been estimated that the precision accuracy of magnetic resonance imaging ranges from 83% －92%［8］.Furthermore，investigators have also reported that T2-weighted imaging generated more accurate information than imaging using contrast enhancement，especially when the female patient has reached the pre-menopausal stage of life.

For most imaging procedures that involve the examination of the abdominal，as well as pelvic area of the female body，the 1.5-T MRI procedure is extensively used，mainly due to the higher resolution that is offered with respect to temporal and spatial assessments.This resolution is technically based on the signal-to-noise ratio that is observed during the imaging.In this investigation conducted by Sadowski et al.［9］magnetic resonance imaging was conducted using a 1.5-T system that was equipped with a surface coil which had a phased-array comprised of four elements.Both T1-and T2-weighted scans were collected to detect any abnormalities within and around the uterus and then transferred to another setup that was equipped with an angiography system supplied with an intravenous tubing.Once the angiography was completed，the patient was transferred back to the magnetic resonance imaging room for the completion of the radiological imaging.Briefly，20 to 40 ml of the contrast media，gadodiamide(1∶100 dilution)dissolved in normal saline solution is injected for image acquisition at various phases using a time-resolved combined T1-weighted magnetic resonance imaging and angiography sequence［9］.Image acquisition is performed using an oblique axial plane that runs through the pelvic regions，thus including the reproductive organs such as the uterus and the ovaries.This procedure proved to be a highly sensitive approach to imaging，with an advantage of allowing the radiologist to perform visualization using a temporal resolution.The study has also been sensitive in detecting any spillage within the fallopian tubes，thus indicating that there are structural abnormalities in these particular reproductive organs.The report of Sadowski et al.［9］thus provides promising results on the utilization of magnetic resonance imaging of the reproductive organs，despite a few allegations that this radiological technique has not been associated with reliable research reports on its applications to uterine imaging［10］.

3.1 Diffusion-weighted magnetic resonance imaging of cervical tumours

Diffusion-weighted magnetic resonanceimaging(DWI)，which derives its contrast from the regional differences in mobility of water molecules is widely used in brain disorders，especially in acute cerebral ischemia.Generally，malignant tumours are depicted as foci of increased intensity on DWI，since water diffusion is restricted in the highly cellular tissue of malignant tumours.Malignant tissue generally exhibits hypercellularity，increased nucleus-to-cytoplasm ratio，and an increase in the amount of macromolecular proteins，resulting in decreased diffusion in the extra-and intracellular compartments［11，12］.DWI can delineate pathologic lesions with high tissue contrast against a generally suppressed background signal.The quantitative measure of DWI is the apparent diffusion coefficient(ADC)that reflects all forms of intravoxel incoherent motion［13］.As ADC is a macroscopic measure，the final measured value results from the contribution of many microscopic factors including cytoskeleton and organelle density，availability of mobile protons and cell density.DWI is further influenced by perfusion from local vasculature，so contributions to the macroscopic ADC will arise from microenvironment variables specific to the tissue in question.Tumour oxygenation(pO2)and interstitial fluid pressure(IFP)are examples of such microenvironment parameters and have been shown to be significant prognostic factors in cervical cancers treated with radiation and surgery［14］.However，it should be noted that impeded diffusion is not specific for malignancy;it can also be exhibited in several benign conditions，including inflammatory and infectious processes［15，16］.Thus，the main value of DWI is expected to lie in the detection and localization of tumours rather than in tumour characterization［17］.It has been reported that diffusion-weighted magnetic resonance imaging can be employed for the quantification of spatial expansion of tumours［1］.Aside from the general uses of all types of magnetic resonance imaging protocols，this particular procedure can also assist in the localization，as well as visualization of specific cellular structures using 3-dimensional reconstruction.The displacement of particular cellular structures can also be considered when the volume of the target tissue is known.Technically，the intensity of signals could be translated as the volume of the target tumour and any areas that have significantly lower intensities may thus be defined as having a smaller volume.The spatial expansion of the tumour is mainly due to the increase in the rate of cell proliferation，as well as a decrease in the diffusion of the contrast media that is incorporated during magnetic resonance imaging.This correlation is influenced by the displacement of cells along the periphery of the tumor，which in turn are the prime sites where the contrast media commonly accumulates during radiological imaging.

3.2 Perfusion magnetic resonance imaging of cervical tumours

Perfusion magnetic resonance imaging can also be employed for the quantification of pharmacokinetic reactions of drugs to the target tumor.There are currently models presenting equations that could precisely calculate the exchange rate of a specific drug，thus indirectly reflecting the volume of blood that is present in that particular region of the tumour.This approach has already been adapted in computerized tomography radiography in assessing cervical tumours，taking consideration of the volume of the gross tumour，the volume of the clinical target and the possible organs that are at risk.In a study conducted by Onal et al.［18］，the volumes of the gross tumour and the clinical target were found to be in an inverse correlation with the size of the tumour，as well as the stage.This observation could therefore assist in the planning for coverage and evaluation of dosages of anti-cancer drugs that should be administered to the patient.

It is possible to estimate the blood flow of a particular region of the target tissue，as well as the mean transit time for this motion.It should be understood that the amplitude of the waves generated from magnetic resonance imaging could be further processed to provide specifications of the circulation of the target tissue.The amplitude of the image signals are therefore in direct correlation with the density of the microvascular system of the tumor，while the exchange rate data could be translated into the extent of permeability of the tumour［19］. These specific parameters collected from perfusion magnetic resonance imaging may thus facilitate in the assessment of the angiogenic potential of cancer tissues.More importantly，these parameters may also be employed for monitoring the response of the tumor to specific anti-cancer treatments.This actual technique has been employed in monitoring the response of tumours to an anti-angiogenic reagent such as thalidomide，which is a drug that shrinks the cardiovascular components that are commonly associated with the etiology of multiple myeloma.

3.3 Combined magnetic resonance imaging and angiography of tumours

Another avenue for the quantification of spatial expansion in cervical and endometrial tissues involves the combination of magnetic resonance imaging and angiography，resulting in the generation of 3-dimensional time-resolved images that are of high-contrast quality［1］.The principle behind angiography is to introduce dyes that are detectable using fluoroscopy and consequently enhanced using contrast media.On the other hand，magnetic resonance imaging focuses on the enhancement of distinct structures within the target tissue of examination.This combinatorial scheme of magnetic resonance imaging with angiography has recently been tested in assessing abnormalities in the reproductive or-gans of women，including the fallopian tubes and the uterus［9］.

3.4 3-T magnetic resonance imaging of cervical tumors

It has been lately reported that 3-T magnetic resonance imaging provides additional advantages that over what is offered using 1.5-T imaging［8］.Among these include a double ratio for signal to noise，greater definition in the spectral range，and higher contrast with respect to the levels of blood oxygenation.It is therefore highly possible that with the superb features of 3-T magnetic resonance imaging，this imaging technique will not only be useful for visual assessments of cervical and endometrial conditions，but also for neurological disorders.It should be understood that employment of higher degrees of magnetic fields may not be directly translated to success in imaging regions of the human body because such changes may also generate a number of restrictions，such as the deposition of radiofrequency waves on the tissue.It is also possible that the duration of T1 relaxation may be increased，and a decrease in the T2 relaxation，as a greater magnetic field is employed during imaging.There is also a possibility that artifacts could arise from the increase in the magnitude of the magnetic field.The enumerated reasons may thus hinder the use of 3-T MRI in imaging studies of the abdominal and pelvic regions of the human body.

3.5 Dynamic four-dimensional(4D)magnetic resonance imaging of cervical tumours

An exciting radiological technique that would facilitate monitoring spatial expansion of tumours is dynamic four-dimensional(4D)magnetic resonance imaging，which technically involves the motion of the tissue over a specific duration of time.Although 4D magnetic resonance imaging is most beneficial to pulmonary tumour and other respiratory conditions，it is also possible to apply this procedure in monitoring the changes that occur within the structural organization of a cervical tumour［1］.Currentreportsusing thisimaging scheme mostly involve intracranial and cardiovascular conditions，focusing on the cellular development and transport of essential proteins and other biological macromolecules［20，21］，as well as processes involving development in other species［22］.Given the high potential of delivering highly informative images for the diagnosis and prognosis of patients with specific medical disorders，it is thus quite easy to assume that a number of applications will be derived from this non-invasive radiological imaging approach.

4 Conclusion

The development of new techniques in cellular and molecular biology has significantly improved the capacity of imaging techniques in visualizing organs and in quantifying the extent of spatial expansion of tumours.Diffusion-weighted magnetic resonance imaging can be employed in examining the cellular dynamics of tumours as it assists in the localization，as well as displacement of particular cellular structures within a particular volume.Perfusion magnetic resonance imaging may be employed for pharmacokinetic reactions of drugs to the target tumour，alongside the calculation of the exchange rate of a specific drug in relation to the volume of blood present in a particular region of the tumour.On the other hand，3-T magnetic resonance imaging presents advantages of double ratio for signal to noise，greater definition in the spec-tral range，and higher contrast with respect to the levels of blood oxygenation.The most recent dynamic three-dimensional(4D)magnetic resonance imaging allows examination of the motion of the target tissue over a specific duration of time.These technologies can significantly improve monitoring schemes on the progress of cervical cancer and assist in the design of treatment programs for oncology patients.

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