MRI TECHNIQUES IN DIAGNOSIS OF PITUITARY DISORDERS

Introduction
The pituitary gland was in the past given various functions by anatomists including being an important source of the phlegm that emanated from the brain to the seat of the soul or the nose. At the beginning of the 20th century, the endocrine functions of the pituitary gland were recognized, and the hormones that were produced by the pituitary gland were identified, and they were classified after their isolation and determination of their structure (Saeed et al., 2014). Harris discovered the role of the hypothalamus in controlling the function of the pituitary gland. The discovery led to the establishment of the neuroendocrinology discipline (Brown et al, 2014). The adult pituitary gland has three lobes that include the anterior, intermediate, and the posterior lobes (Avis, Fisher & Warach, 2003). The anterior and the intermediate lobes of the pituitary gland have a common developmental origin from the ectoderm. The extension of the hypothalamus or the ventral diecephalon forms the posterior lobe of the pituitary gland. The intermediate pituitary is made up of a homogeneous tissue that has the melanotroph cells. The melanotroph cells produce the alpha-melanotropin hormone (Saeed et al., 2014). The anterior lobe of the pituitary gland has about five hormone secreting lineages. The lineages consist of the gonadotropes, the corticotropes, the somatotropes, the lactotropes, and the thyrotropes (MacMaster & Kusumakar, 2004). The corticotropes produce the adrenocorticotropin hormone (ACTH), while the gonadotropes produce the follicle stimulating hormone (FSH) and the luteinizing hormone. The somatotropes produce the growth hormone while the lactotropes produce the prolactin hormone. The thyrotropes produce the thyroid-stimulating hormone. The posterior lobe of the pituitary gland has the axonal projections of the hypothalamus whose function is to secret the oxytocin and the vasopressin. The intermediary lobe of the pituitary gland is found in many species including the rats, rodents, and mice, but in humans it regresses in the 15th week of the gestation. The intermediate lobe in humans is thus absent. The mice have been used in the past and present to study the pituitary functions in humans. The pituitary gland is often faced with various disorders like any other organ in the human body (MacMaster & Kusumakar, 2004). Most of the disorders that are found in the pituitary gland are the occurrence of tumors that affect the normal functioning of the pituitary gland. The tumors are normally referred to as the pituitary adenomas, and they vary widely in size. The tumors affect the normal functioning of the pituitary gland by compressing the surrounding structures, and interfering with the secretor function of the pituitary gland. The tumors vary in sizes but most of them are very small (3to 5mm). The tumors can sometimes be very difficult to diagnose because of their small size. The other disorders that affect the pituitary gland are the occurrence of lesions in the regions that are adjacent to the pituitary gland. However, many of the lesions are not life threatening (Vlaardingerbroek, Boer & Luiten, 2003). The clinical processes that are involved in the detection of the pituitary disorders are not adequate to diagnose the pituitary adenomas especially in the situations where the patients present with other symptoms such as headache and visual impairment. Therefore, the clinical processes such as the use of the computerized tomography techniques have not been effective enough in the diagnosis of the pituitary disorders (CARLSON & CHANG, 1980). It is for this reason that the medical experts choose to use the magnetic resonance imaging techniques to detect the presence of pituitary disorders in humans. The magnetic resonance imaging techniques have been used in the past and present to produce the detailed images of the sections of the brain, and the pituitary gland. The magnetic resonance imaging is widely preferred than other imaging mechanisms that use highly penetrating radiations that are harmful to the human body because they kill the human cells. Radiations such as the x-rays are used to produce images of the internal organs of the human body. X-ray is harmful to the cells of the body if used in large doses or when used repeatedly. The repeated exposure of the x-rays to the human body is not medically recommended (CARLSON & CHANG, 1980). The magnetic resonance imaging techniques uses the pulses of radio wave energy and the magnetic field to produce the images of the internal organs of the body. In most cases, the MRI gives detailed information about the structures of the body that cannot be seen using other methods such as the x-ray, ultrasound or the scan using the computerized tomography mechanism. In this study, the role of the magnetic resonance imaging in detecting the various disorders of the pituitary gland will be examined.
Aims and objectives of the study
To determine the role of the magnetic resonance imaging in detecting the pituitary disorders
To determine the differential diagnosis of pituitary adenomas, Rathke cleft cysts and craniopharyngiomas using the magnetic resonance imaging techniques.
To determine the features of the disorders that enables their detection in the MRI
To determine how dynamic MRI is useful in detecting the lesions around the pituitary gland.
To determine the usefulness of contrast media in visualizing the pituitary adenomas
Literature review
Epidemiology of pituitary disorders
The most common pituitary disorders are the pituitary tumors. Currently there is not much data that addresses the prevalence of the disorders of pituitary gland. The pituitary tumors are considered to be rare, and the radiologic and autopsy studies have revealed a prevalence of 17% in the population. The tumors affect both sexes equally. In addition, the pituitary tumors are rare in children, and more common in adults. Therefore, the tumor cases increases with age. The most common types of adenomas are the prolactin-producing adenomas (James, 2015). One third of the tumors are not associated with the hypersecretory syndromes. Most of these tumors produce (but not secret) the Gonadotropins FSH hormone or the luteinizing hormone. The ACTH-producing tumors and the growth hormone producing tumors have a prevalence of 10 to 15% each. The activity of hormones is used to classify the pituitary tumors. The acth-producing adenomas are closely associated with Cushing’s disease while the GH-producing tumors are associated with gigantism and acromegaly. The pituitary adenomas that produce prolactin cause hyperprolactinemia. The tumors that produce TSH are closely associated with the dysfunction of thyroid. The gonadotroph adenomas are rare. The incidental pituitary tumors occur in about 10% of the autopsies. Acromegaly has an incidence of 3 per million, and it lacks sex predilection. The incidence of pituitary adenomas is the same worldwide. The mortality rate that is associated with pituitary tumors is very low (James, 2015). The advances in the surgical and medical management of the tumors or lesions, and the hormone replacement therapies have made the management of the tumors to be successful. The morbidity of macroadenomas includes the ophthalmoplegia and visual loss. Tumors have the potential to recur. The distant metastases and the CNS metastases are known to occur with the pituitary tumors. The symptomatic prolactinomas are common in women. The Cushing’s disease is also common in women than in men (the ration of female to male is 3to 1). Pituitary adenomas are common in young adults although they may be found in adolescents and elderly people. Acromegaly occurs mostly in the fourth or the fifth decade of life.
Anatomy of pituitary gland
A pituitary gland that is fully developed has the size of a pea, and it has a weight of 0.5g. Large part of the pituitary (about 80%) consists of the adenohypophysis, and it produces various peptide hormones. The hypothalamic neurohormones mediate the release of the pituitary hormones that are secreted from the median eminence (place where the axon terminals rise from the hypothalamus).

Figure (a) sagittal section of the pituitary gland. Retrieved from http://emedicine.medscape.com/article/1899167-overview#a2
The adenohypophysis is glandular unlike the neurohypophysis. The neurohypophysis does not manufacture hormones (James, 2015). The neurohypophysis is where the axons arise from the neuronal cell bodies in the paraventricular and supraoptic nuclei of the hypothalamus. The hypothalamic cell bodies have a function of producing hormones that are transported via the pituitary stalk, and go to the terminal axons in the neurohypophysis. The hormones are stored, and then released to the systemic vasculature.
The dura envelops the pituitary gland that is found within the sella turnica of the sphenoid bone. The sella turnica is a depression that is saddle-shaped, and surrounds the inferior, anterior, and posterior sections of the pituitary gland (James, 2015). The diaphragma sellae covers the superior section of the pituitary. The diaphragma sellae is a fold of the dura mater, and it separates the pituitary from the cerebrospinal fluid-filled subarachnoid space. The diaphragma sellae is pierced by the infundibulum to enable the connection of the pituitary to the hypothalamus. Laterally, the pituitary is adjacent to cavernous sinuses as shown in the figure (b) below. From superior to inferior the cavernous sinus constitutes of the cranial nerves III (oculomotor), IV (trochlear), and VI (abducens). The cavernous sinus also has the cranial nerve V1 or the ophthalmic branch of trigeminal nerve, and the cranial nerve V2 also known as the maxillary branch of trigeminal nerve. The cranial nerves are shown in figure (b) below.

Figure (b) The coronal image of pituitary gland, and the adjacent structures. Lateral aspect of the pituitary gland the cranial nerves. Retrieved from http://emedicine.medscape.com/article/1899167-overview#a2
The location of the sphenoid sinus relative to the sella turnica is described by the various patterns of pneumatization of the sphenoid sinus (presellar, sellar, conchal and postsellar). The patterns determine the degree of exposure of the sellar floor. Pneumatization is not found in the conchal type, and air cavity is absent in the sphenoid sinus. The posterior extension of air cavity is little in the presellar type.
Vasculature
The paired superior hypophyseal arteries supply the adenohypophysis with blood. The artery emanates from about 5mm distal to the region of origin of the ophthalmic artery (James, 2015). The artery forms the primary network of capillaries in the median eminence. The inferior hypophyseal arteries supply the neurohypophysis with blood as shown in figure (c) below. The vessels are terminal branches of meningohypophyseal trunk that emanates from cavernous portion of the internal carotid artery.

Figure © vasculature of pituitary gland showing neurohypophysis and adenohypophysis. Retrieved from http://emedicine.medscape.com/article/1899167-overview#a2

MRI sequences
The magnetic resonance imaging is an important method that is used to view the pituitary adenomas. The MR technique enables the soft tissue contrast, has a good spatial resolution, has no beam hardening because of the adjacent bone, and it enables the detection of the gland in multiplanar images. The best conventional sequences that are used include the thin section T1 weighted coronal, and the sagittal SE images prior and after the injection of the contrast material. The T1- weighted images show the anatomic details of the pituitary clearly (Yuksekkaya et al., 2014). The lesions are also visible as atypically hyperintense in the T1-weighted images that are enhanced with IV-GBCM (Yuksekkaya et al., 2014). When the dose of Gadolinium is too high or the window of visualization is large the T1-weighted images may be negative. In addition, when the tumor is too small, the images may be negative. An example of the T1 weighted image of pituitary is shown in the figure (d) below.

Figure (d) shows the T1-weighted coronal, and the sagittal images that are enhanced with IV-GBCM. The invasion of the right cavernous sinus is shown on the T1 images. Image retrieved from http://www.hindawi.com/journals/isrn/2014/650926/#B2
The T2- weighted coronal images are useful in screening the pituitary gland, while the T1 weighted images are used to characterize and to confirm the abnormalities. The T2 weighted coronal images are used as a guide. A study has shown the T2-weighted coronal images having a sensitivity of 68.7% in the detection of adenomas (Yuksekkaya et al., 2014). The study showed that a high specificity of 100%, and a low specificity of 68.7 rates in the T2 weighted coronal image was possible. The T2-weighted images were used to observe various lesions without the administration of IV-GBCM. The T2-weighted images have an improved visibility of the pituitary adenomas, and the ancillary MR imaging signs. The t2-weighted coronal images are easy to perform, and they do not require the administration of IV-GBCM. The images are used for the primary investigation of the pituitary gland. The T2-weighted coronal image is shown in figure (e) below.

Figure (e) shows a t2-weighted coronal image. The image shows a suspicious lesion that is hyperintense on the left side of the pituitary gland. Image retrieved from http://emedicine.medscape.com/article/1899167-overview#a2
Gradient echo sequence
This is the simplest type of MRI sequence. The sequence has a series of excitation pulses that are separated by repetition time TR. When the application of the excitation pulses is done, the data is then obtained. This called the echo time. The echo time (TE) is defined as the time between midpoint of the excitation time, and the midpoint of the acquisition of data. This is shown in the sequence diagram figure 6-1 below. The contrast of the image varies with the changes in TE and TR. In the K-space representation, the application of both the read diphase gradients and the phase encode leads to the translation from the centre of k-space from A to B. The process is followed by the encoding of frequency from B to C via the K-space centre. The figure 6-1 below shows the gradient echo principle in sequence 1.
Figure 6-1 shows the gradient echo sequence. Image retrieved from http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/chapter5.pdf

Spin echo sequence
The spin echo sequence (SE) bears some similarity with the GE sequence, except that there is another 180° refocusing pulse in the sequence. The pulse is halfway between the echo and the excitation pulse as shown in figure (5-3) below. After a 90° RF pulse, the vector of magnetization lies in a transverse plane. The application of the 180° pulse enhances the flipping of the spin vectors such that the initially slower vectors precede the initially faster ones. Following a time delay of TE/2, a spin echo is formed as shown in figure 5-3 below.

Image retrieved from http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/chapter5.pdf
The application of the read dephase gradients and the phase encoding leads to the movement from the centre of k-space A to B in the k-space representation of the spin echo sequence. The pulse of180º leads to the reversal of the k-space position in both the frequency directions and the phase. This leads in the movement from B to C. The process is then followed by the frequency encoding from C to D through the centre of the k-space. As shown in figure (5-4). Each data line undergoes a Fourier transformation to extract the frequency information in the signal. The process occurs repeatedly in the various phase encode steps. Figure 5-4 shows how a spin echo sequence is formed.

Figure 5-4. spin echo sequence and the( R) k-space representation. Image retrieved from http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/chapter5.pdf
Inversion recovery sequence
This is an SE sequence variant that starts with a 180º inverting pulse. The process leads to the inversion of the longitudinal magnetization vector through the 180º. After the removal of the inversion pulse, the vector of magnetization starts to relax back to B0 as shown in the figure 5-5 below. The 90º excitation pulse is applied after sometime since the application of the 180ºinverting pulse that is called the time to inversion or TI. The length of TI together with TR and TE determines the contrast of the resulting image. The magnitude of the longitudinal magnetization plays a significant role in the creation of contrast in the image after a chosen time of delay TI as shown in the figure 5-6 below. The figure 5-7 shows the complete inversion recovery pulse sequence.
Figure 5-6 shows the T1 weighted diagram for water and fat protons in the inversion recovery sequence. Image retrieved from http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/chapter5.pdf

Image retrieved from http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/chapter5.pdf
Short TI inversion recovery (STIR) sequence
This is an inversion recovery pulse sequence that uses a TI that has correspondence with the time taken for fat to recover from the full inversion to the transverse plane. The process ensures the absence of the longitudinal magnetization that corresponds to fat. After the application of 90º excitation phase following the delay time TI, the fat signal is nullified. The STIR is very useful in the suppression of the fat signal in a T1 weighted image. In most cases, a TI of 150 to 175ms is used to suppress fat signal. However, the value depends on the field strength used (for example 140ms in the 1.5T scanner). The figure 5-8 shown below expresses how the STIR sequence uses the short TI to suppress the fat signal in the T2 weighted image.

Image retrieved from http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/chapter5.pdf
Gadolinium DPTA contrast material
The Gadolinium DPTA/dimeglumine is a contrast agent that is paramagnetic, and has the capacity to differentiate tumor from edema in the intracranial tumors. The efficacy of Gadolinium DPTA in defining the pituitary tumors is largely unknown. In the invivo environment, the Gadolinium contrast material is handled in a similar manner to the iodinated contrast material. Therefore, the Gadolinium is very useful in the process of improving the accuracy of MRI in pituitary adenoma detection. Key questions involving the use of gadolinium in MRI imaging and detection of pituitary adenoma include its usefulness in detecting chiasmal compression, detecting the focal lesions, detection of cavernous sinus invasion, and the diaphragm sellae abnormalities. Another important question concerns the right dosage to be used in MRI detection of pituitary adenomas. The gadolinium dose that is used is 0.1mM/kg. The dose is small enough to bring about the required enhancement of the tissue. Too much dosage can lead to the enhancement of the surrounding tissues thus reducing the detection capacity of MRI process.
TR and TE
The imaging of pituitary gland requires the use of multiple RF bursts together with the signal recordings or pulse sequences. The spin echo imaging is currently the favorable technique. In the spin-echo imaging, the period between the repetitive cycles (TR) is varied within a wide range. The same occurs in the time between the signal recording (TE), and the excitation pulse. In the spin echo technique the intensity of the signal depends largely on the density of the proton or the hydrogen nuclei, and the flow (f). The relationship between the factors is given by the tissue, and the TE and the TR are controlled by the operator. The shortening of the TR increases with the T1 influence on the contrast. The lengthening of the TE increases the influence of the T2. The pulse sequences that have short TR and TE such as 300 and 30ms are T1 weighted. The pulse sequences that have long TR and TE such as 1500 and 120ms respectively are T2 weighted. The pulse sequences that have long TR and short TE are called mixed sequences. In case no flow is present, the intensity of the signal is influenced by the proton density. The spin echo imaging that has two echos e.g 30ms and 120ms, a long TR (1.5 to 2.0s), and a slice thickness of 5 to 10 mm is enough to image most microadenomas.

Figure 3 shows TR and TE images of pituitary. Image retrieved from http://emedicine.medscape.com/article/1899167-overview#a2
The magnetic resonance imaging is widely used to show the presence of small pituitary tumors. The MRI technique is more effective than the computerized tomography method. The detection of the small tumors in the pituitary gland is greatly improved by the use of paramagnetic contrast agents such as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). In some instances high levels of detection of pituitary tumors have been recorded without the use of the paramagnetic contrast agents. Kucharczyk and his colleagues conducted studies in which they used a 1.5 T magnet to show the presence of the pituitary microadenomas without using the paramagnetic contrast agents. The researchers were able to show more than 90% of the pituitary microadenomas. The findings gave a promising result, and increased the reliability of the magnetic resonance imaging in detecting the pituitary microadenomas and other small pituitary tumors. The pituitary adenoma that is not complicated usually shows a signal that parallels the grey matter in the MRI imaging. In addition, the MRI imaging shows other enhancement patterns and signals that are associated with conditions such as hemorrhage, necrosis and cystic degeneration. The magnetic resonance imaging is also widely used to carry out a differential diagnosis in the tumors that involve the intrasellar and the supracellar regions. The differential analysis that takes place in these regions involve the Rathke cleft cyst, pirtuitary adenoma, and the craniopharyngioma. The differential analysis is conducted when a lesion involving the intrasellar and the suprasellar regions is encountered. The findings of the differential analysis are used by neurosurgeons to plan the surgical process. The pituitary adenomas are usually approached using the trans-sphenoidal route while the craniopharyngiomas are approached by radical surgery and craniotomy. The symptomatic Rathke cleft is approached using the surgical drainage method accompanied by the partial excision of the wall of the cyst. However, it is not easy to make a differential diagnosis of the three tumors using the magnetic resonance imaging techniques especially in the situations when the tumor has cystic or solid characteristics. The diagnoses of the three tumors using other clinical procedures becomes complicated more in case the patients present with cases that are not clear such as visual disturbances, headache, and hypopituitarism. In contrast, it is easier to diagnose the three tumors using the MRI findings because of the characteristics they have on the MRI method of diagnoses. The pituitary adenomas with the suprasellar extension are easily recognizable because they have an appearance of figure eight (snowman appearance)and they are enhanced the most among the three types of tumors. This is a very important feature that enables the recognition of the pituitary adenomas using the magnetic resonance imaging technique. In the literature, there are two histological types of craniopharyngiomas that include the adamantinous and the squamous papillary types although in some cases it is difficult to divide the craniopharyngiomas into the two distinct histological types. On the magnetic resonance imaging the squamous-papillary craniopharyngioma has special features suchas the presence of a predominant cystic, solid or mixed solid tumor that is located in the suprasellar region. The adamantinous craniopharyngioma is usually a cystic, lobulate tumor that is found in the suprasellar or the intrasellar regions. In the T1 weighted images, the presence of multiple or single hyperintense cysts that have thin peripheral enhancing rims indicates the presence of adamantinous craniopharyngioma.The image features that confirm the presence of Rathke cleft cysts in MRI imaging include the presence of a sellar epicentre, lack of calcification, smooth contour, lack of internal enhancement, and the presence of a homogeneous signal intensity in the lesion. Despite the presence of the many differentiating characteristics of the tumors in the magnetic resonance imaging, it si still difficult to distinguish between the subset of the tumors. The shapes of the three tumors are different in the magnetic resonance imaging and this is an important feature that is used to distinguish between the tumors. In addition, the tumor extents and volumes are unique among the three tumors, and this feature is also used to distinguish between the three tumors. Many pituitary adenomas arise from the pituitary gland and then extend to the diaphram sella and to the optic chiasm. On the other hand, many craniopharyngiomas crop up from the suprasellar region and then reach out to the third ventricle and then to the intrasellar region. The Rathke cleft cysts crop out from the pituitary fossa, and they have a major characteristic of having small volumes because of their small extents. According to Chai et al, the characteristics of tumor and the enhancement patterns can be helpful in the creation of flowcharts that can be used for diagnoses of the three tumors. According to the research that was done by Chai et al, the component characteristic of the three tumors was the most accurate feature of the Magnetic resonance Imaging. In the research, about 43 of the total 64 patients were diagnosed with each tumor using the typical component characteristics. According to Chai et al, the specific feature of the enhancement pattern of the solid portions of the three tumors was the most recognizable in the findings of the magnetic resonance imaging. The level of accuracy of the enhancement patterns of the solid portions of tumors in the MRI imaging was 96%. The findings had a meaning that about 43 of the total 45 patients were diagnosed of the tumors using the enhancement patterns of the solid portions. The findings show that the MRI can be a very accurate method of distinguishing between the different types of tumors in the pituitary gland. According to the Chai eta al, the cyst wall enhancement pattern was the most reliable MRI finding that was used to distinguish the cystic tumors from the Rathke cleft cysts. The solid characteristics were very helpful in diagnosing the pituitary adenomas. The research by Chai et al, further states that the homogeneous enhancement patterns are very accurate in the differential diagnosis of the pituitary adenomas that contain the solid elements. The reticular enhancement patterns are very effective in the differential diagnosis of craniopharynginomas. A previous study has shown the occurrence of squamous-papillary craniopharynginomas that have the homogeneous enhancing solid masses. However, in the study that was conducted by Chai et al, the craniopharynginomas that have the solid elements showed a reticular enhancement pattern. Other published literature suggest that the reticular enhancement pattern of the solid containing craniopharynginomas result from the small regions of keratin debris, calcification or minute regions of necrosis. The cyst characteristic is highly accurate in the differentiation of the Rathke cleft cyst from other tumors. The presence of the thin cyst wall or the lack of the cyst wall enhancement pattern is a major finding of the magnetic resonance imaging that is used to differentiate the Rathke cleft cyst from other cysts such as the neoplastic cysts that are found in the suprasellar and the intrasellar regions. The findings from the current studies have suggested that the squamous metaplasia, deposition of cholesterol crystals and haemosiderin in the cyst wall, and inflammation could be the cause of the occurrence of the thin rim of the peripheral enhancement of the Rathke cleft cysts. The cystic portions of the Rathke cleft cyst are far thinner than the cystic portions of the craniopharyngioma and the pituitary adenoma. The feature is very useful in the differential diagnosis of the Rathke cleft cyst and the pituitary adenoma. The cystic portions of the tumors are thought to contain the components of hemorrhage, necrosis, and the cystic degeneration of the pituitary adenoma. Cholesterol, high concentration of protein, and methaemoglobin are the main compositions of the Rathke cleft and the craniopharynginoma cysts.
The magnetic resonance imaging is also widely used to diagnose lesions that are adjacent to the pituitary glands. The dynamic Magnetic resonance imaging is useful in the evaluation of the parasellar lesions that are non-neoplastic.

The epidemiology of the pituitary tumors has shown the incidence of between 3.2 to 27% in the postmortem series and an average of 10%. A study was done on more than 3000 autopsied pituitaries. In the study it was found that a significant number of the tumors are only for the pathologists or subclinical tumors. The rest of the tumors (1/600 to 1/1000) are actually macroadenomas. The evaluation that was done using the high resolution imaging such as the computerized tomography with contrast for reasons that were not related to the disorders of the pituitary gland revealed the hypodense lesions in 10 to 25%. When the magnetic resonance imaging was used to visualize the brain, a pituitary mass about 10% was revealed without contrast. In a meta analysis that was conducted recently, the prevalence of the pituitary adenomas was revealed. The prevalence of the pituitary disorders was found to be 14.4% in the postmortem studies while in the radiological studies the prevalence was found to be 22.2%. The overall prevalence rate was found to be 16.9%. The imaging technology has drastically changed the way the pituitary tumors are managed. Today, it has been known through research that the sellar mass can harbor many lesions that are found adjacent to the pituitary adenomas. Some of the pituitary lesions have been found to have no effect on the health of the individuals and they are called incidentalomas. The lesions are harmless because they do not affect the normal functioning of the pituitary gland, and they do not invade or compress the surrounding areas (Macpherson, Hadley, Teasdale & Teasdale, 1989). Therefore, the lesions do not require the medical attention in most cases (Suzuki et al., 2005). When many patients are informed that they suffer from a pituitary adenoma, their anxiety grows even if they do not experience any symptoms, and their pituitary function is normal. Many medical physicians consider the incidentalomas of the pituitary gland for further sequential follow-up. The occurrence of a neoplasia affects the normal functioning of the cell, such as the lack of normal control of the cell cycle that can result from the loss of heterozygosity of the tumor suppressor genes or the oncogene activation. Today, there is a significant progress in the molecular pathogenesis of the adenomas of the pituitary gland (Stoller & Ovid, 2007). The stem cells have been used as significant sources of tissue renewal. The stem cells are also a significant source of the monoclonal proliferation under certain environmental conditions and with the help of a favorable genetic background (Buxton, 2009). The pituitary adenomas represent a wide variety of disorders that can be classified and analyzed in accordance to the autonomous secretion, clinical procedures of diagnoses and treatment, pathology that is determined using the electron and the light microscopy features, and other pituitary issues. The rare pituitary carcinoma cases and the pituitary adenomas can result to the death of the victim especially in the cases when they lead to compression or local invasion. The conditions can also be life threatening when they lead to the metabolic or cardiovascular complications. The World health organization has developed a classification system that integrates the operative findings, imaging, detailed pathology, and the endocrine activity (CARLSON & CHANG, 1980). According to the classification system of the World Health Organization, there are three types of anterior lesions of the pituitary gland. The lesions include the typical pituitary adenoma, the atypical pituitary adenoma, and the pituitary carcinoma. The tumor markers have been used to classify the pituitary tumors. The labeling index known as the Ki-67 is used for classification primarily because of its strong correlation with prognosis and the tumor invasiveness. The adenomas that show an increased labeling index together with extensive p53 immunoreactivity are normally classified as atypical adenomas. The atypical adenomas have the malignant transformation or aggressive potential. The term pituitary carcinoma is used only when the systemic or the cerebrospinal metastases are identified. It is important to classify the tumors first in order to determine the ones that require medical attention. Many of the tumors are incidentalomas that do not require further medical attention (MacMaster & Kusumakar, 2004). The detection of the pituitary adenomas gives the neurosurgeon the need to conduct detailed diagnoses, and provide pharmacological aid or radiation therapy (Macpherson, Hadley, Teasdale & Teasdale, 1989). In other cases, a surgical procedure may be required for treatment. The technical facilities, variation in human resources, and the financial constraints can affect the detailed classification and analysis of the pituitary tumors.
The magnetic resonance imaging techniques have been used in the past to study various aspects of the pituitary gland and the brain in general. The MRI techniques have been used in the past to study the pituitary volume in teenagers during puberty where they have revealed the sudden growth of the pituitary volume during puberty. The MRI findings have also recorded the decrease in the pituitary volume as the age of the teenagers’ progresses. Previous studies that have been conducted on the pituitary glands have shown that the endocrine abnormalities partly result from the changes in the morphology of the pituitary gland. The size of the pituitary gland differs with the sexes, and the women have larger pituitaries than men. In the women, the pituitary gland continues to increase during the pregnancy period, and the early post partum period. The hypothalamic pituitary adrenal axis has been recorded in the past especially in the cases of depression. The MRI studies have been conducted to examine the volumes of the pituitary gland during the psychiatric illnesses. Previous studies have reported the increase in the pituitary volumes in the patients who have great alcohol dependence (Lanctôt, Gauthier & Drouin, 1999). In bulimic patients the reduction of the pituitary volumes has been noted. The MRI findings are used to determine the abnormalities in the sizes of the pituitary gland, and the possible diagnoses of a pituitary disorder. Due to the small size of the pituitary gland, the imaging that uses a high spatial resolution is useful for the detection of the small lesions such as those that are found in the cushing’s disease. A high resolution of 7.0 Tesla has been successfully used in the past to detect the small lesions.
The clinical classification and presentation
In the process of clinical presentation, the pituitary adenomas are classified as either secreting tumors or adenomas that are clinically non functional. The secreting tumors include the adrenocorticotropic hormone (ACTH), prolactin hormone in women, growth hormone, and the thyroid stimulating hormone (TSH). The secretion of the tumor allows for easy testing because it leads to various clinical syndromes. Apart from the secretion of the tumors, the pituitary adenomas lead to the compression of the surrounding structures, and the condition leads to the cavernous sinus syndrome, invasion of the sphenoid sinus, and the extension to the base of the brain. The normal functioning of the pituitary gland can be impaired leading to the failure of the pituitary gland. The prolactin secreting tumors are the most common, and they account for about 30 to 35% of all the reported cases of pituitary tumors. The adenomas that secret the growth hormone usually result to the acromegaly condition and gigantism. The adenomas that secret the ACTH hormone are the least common, and they cause the cushing’s disease. The tumors that secret the thyroid stimulating hormone lead to the pituitary hyperthyroidism. The other pituitary adenomas that do not fall in the above category form about a third of the known tumors, and are called the nonfunctioning pituitary adenomas (NFPAs). The symptoms that result from the nonfunctioning pituitary adenomas are mainly due to the growth of the tumor. Gonadotropinomas (tumors that secret mute hormones), and the null cell adenomas (tumors that have no immunoreactivity) are only subdivided after a detailed immunopathology is done. The current magnetic resonance imaging techniques have the capacity to identify half of the ACTH secreting tumors. The sensitivity of the magnetic resonance imaging is very high for the microadenoma detection, reaching the levels of over 85% with the use of the normal conventional techniques. The use of the dynamic MRI in the detection of the microadenomas increases the accuracy of detection by about 5 to 10%. The detection of the microadenoma using the dynamic MRI is faced with some challenges such as the generalized glandular enhancement after the administration of the contrast material. The generalized enhancement makes it difficult for the medical physicians to differentiate between the normal glandular tissue and the microadenomas. The identification of the ACTH secreting tumors becomes more difficult because of their localization and their ventrally located size. In addition, about half of the tumors that secret ACTH are very small (about 5mm or less). The sensitivity of the MRI in the ACTH-secreting tumors differs widely among various researchers. However, most researchers admit that the MRI techniques only succeed in detecting about half of the ACTH-secreting tumors. The traditional mechanisms that employ the use of dynamic MRI have about five sets of images that are obtained after the use of gadopentetate dimeglumine. PSS is normally used for the diagnosis of the ACTH-secreting tumors, but its complexity and expensive nature makes the MRI method to be the most favorable method to detect the ACTH-secreting tumors. However, the capacity to detect the tumors differs from one patient to another, and it is even more difficult to use PSS to detect the ACTH-secreting tumors in some patients (Marziali et al., 2004). The successful treatment of the ACTH-secreting tumors requires a great improvement in the magnetic resonance imaging techniques, and accurate localization (CARLSON & CHANG, 1980). Research has shown that the use of the 3-T MRI together with a half-dose contrast improves the accuracy of the sensitivity for the tumors of the brain than the 1.5 Tesla. There are no current studies that have involved the use of half-dose contrast materials in the dynamic 3T in the detection of the microadenomas of the pituitary glands. The full-dose contrast could have the disadvantage of improving the enhancement of the glandular parenchyma, a condition that leads to the increase in the signal intensity of the normal pituitary tissue. The process it difficult to differentiate between a normal tissue and a pituitary tumor.
Method
The method that is going to be used in this research will involve the use of the magnetic resonance imaging techniques to test the accuracy of the technique in diagnosing various pituitary disorders. In this clinical research, the GadoLinium diethylenetriamine pentaacetic acid will be used to improve the recognition of the various disorders using the MRI imaging technique (Lanctôt, Gauthier & Drouin, 1999). The imaging technique will be performed to eight patients who have surgically proven pituitary micro adenomas and other pituitary conditions. The process of recruiting the patients for the medical research will be done in accordance with the medical laws that guide the individual health information. The law requires that the patient gives his / her consent to be recruited for the study. The law also requires the patients consent before his /her medical information is shared with the researcher. The approval by the patients will be in the form of written consent and will be obtained by the researcher prior to the commencement of the research. The rationale behind the choice of patients with proven pituitary disorders is because the researcher will be able to accurately determine the effectiveness of the Magnetic Resonance Imaging technique in diagnosing the pituitary disorders (Lanctôt, Gauthier & Drouin, 1999). The researcher will have prior knowledge about the condition of the patients and will therefore be in agood position to test whether the technique can be used to diagnose the conditions. The researcher will obtain the medical records of the patients in accordance with the law and determine the suitable patients for recruitment in the study. The patients who will be recruited for the study will be between the ages of 22 to 50 years. The mean age of the patients will be 33 years (Marziali et al., 2004). The 1.5T scanner will be used for the study, and it will have a 3mm contiguous slices. In the research, theshort repetition times, the long repetition times, short echo times and the long echo times sequences will be obtained before and after the use of the Gd-DPTA. The patients to be recruited for the study will be required to have an ACTH-dependent hypercortisolism and a positive dexamethasone suppression testing. The patients will also be required to have a positive CRH simulation testing together with an increased level of ACTH in the petrosal sinuses in comparison with the peripheral levels prior and after the intravenous CRH injection. The patients will also be required to have a negative contrast enhanced coronal CT. The TR of 600 ms, and a TE of 20ms together with two acquisitions will be used to obtain the coronal 3mm interleaved slices. The field of view that will be usedin this study will be 16 centimeters together with 256 phase encoded steps. The TR of 2000 ms, 16cm field of view, a TE of 80 ms, and two acquisitions with 128 steps will be used to obtain the long TR and the long TE. The intravenous administration of Gd-DTPA will be conducted followed by the T1 weighted sequence SE 600 / 20 that will be repeated severally in the order of 3 to 10, 20 to 30 and 30 to 70 minutes (CARLSON & CHANG, 1980). The T2 weighted scans will also be obtained in all the patients in 10 to 20 minutes at SE 2000/80. During the study, the site, size and the extension of the micro adenoma will be recorded by the researcher. The consistency of the micro adenoma will also be determined and it will be classified as either semi liquid or solid. The distinction of the adenomas will be based on whether the adenoma produces a fluid after the incision of its capsule. If the adenomas will be identified in the patients they will be resected where possible. In case the tumor is found to have developed much, the patient with the tumor will be subjected to a radiation therapy. In the patients who the micro adenoma will not be identified the neuro surgeons will perform hemihypophysectomies in the side that has more ACTH gradient. The evaluation of the consistency and the size of the adenoma will relymore on the description and measurements that will be given by the researcher.
Differentiation of craniopharyngioma, Rathke cleft cyst and pituitary adenoma using MRI
The research methodology will also focus on the determination of the capacity of the Magnetic resonance imaging techniques to differentiate between the three tumors that are common to the patients who suffer from pituitary disorders (Choi et al., 2007). The researcher will begin the study by first searching the pathology data base of patients who suffer from craniopharyngioma, Rathke cLeft cyst and pituitary adenoma from the year 2002 to the year 2014. The researcher will access the database with the permission from the necessary authorities and in accordance to the privacy law. The individual consent for the obtaining of the health data will not be required because the researcher will get anonymous data that may involve the use of codes to protect the identity of the individuals. The researcher will use the basic search methods using the keywords on a computer. The keywords that will be used for this search are the Rathke cleft cysts, pituitary adenoma and the craniopharyngioma. The researcher will go through hundreds of the patients’ data to identify the potential recruits for the study and to exclude the patients who do not qualify for the study (Marziali et al., 2004). The patients who will be excluded for the study are the ones who the MRI was not performed or the ones whose MRI images are not available. The patients whose pathological examination showed that they suffered from various diseases will also be excluded for the study .In addition, the patients who received biopsy or surgery prior to the MRI process will not be included for the study. The remaining patients after the exclusion process will be included in the study. The patients that will be included for this study will have a mean age of 40 years and they will be 40 or more (Choi et al., 2007). The approval by the institutional review board will not be sought after and the informed consent will not be required because the anonymity of the patients will be maintained. The MRI will be performed using the 1.5T MRI machine. The imaging sequences will include the sagittaL, T1 weighted, T2 weighted, and the contrast enhanced T1 weighted coronal and sagittal sequences that will be produced at 30-60s following the intravenous bolus injection of 0.1mmoL/kg gadopentetate dimeglumine. The section thickness will be 5mm and an intersection gap of 0.5mm will be used. The spin echo T1 weighted images will be obtained at 440 to 650ms/8 to 24ms. The fast spin echo T2 weighted images will be obtained at 4000 to 5000 ms/96 to 122 ms. The MRI images will be reviewed on the picture receiving and communication system.
Diagnoses of lesions that are adjacent to the pituitary gland
The Magnetic resonance imaging techniques can also be used to diagnose the lesions that are adjacent to the pituitary gland as it has been shown in previous research findings. Various methods that have similarity to the previously discussed methods will be used to test the effectiveness of the MRI in the diagnoses of lesions that are adjacent to the pituitary gland. The research method that will be applied in this situation will comprise the examination of 13 tumors (Macpherson, Hadley, Teasdale & Teasdale, 1989). The tumors will be made up of seven meningiomas, cavernous hemangiomas and other types of tumors. The 1.5 T signa horizon will be used to get thin coronal, slice sagittal, and the axial T1-weighted images of the sellar regions. In the sagittal and the coronal dynamic studies, the Fast spin echo sequences will be used. The TR will be 400 to 500 ms while the TE will be 7.5 to 20. In addition, the echo train length will be four. The parameters that will be used for this study will be 256*128, slice thickness of 2 to 5 mm, and one excitation. The scan time will be approximately 18s. Several sequential images will be obtained after the intravenous bolus injection of the contrast media. After obtaining the images, the capacity of the images to give precise information that can lead to the differentiation between the tumors and the pituitary gland will be evaluated.

Results
Evaluation of the MRI findings
The evaluation of the MRI findings will largely be based on the previous research that has been approved by the scientific bodies of medicine and neurosurgeons. From the evidence based sources it is known that the pituitary adenomas, Rathke cleft cysts and craniopharyngioma have special features in the MRI that differentiate them from one another. The shape that is expected to be seen in the MRI for the pituitary adenoma is a snow man appearance as shown in the figure below, while the shape that will be expected for the craniopharyngioma is superior lobulation. The shape that will be seen for the Rathke cleft cysts is ovoid. The Rathke cleft cysts will be expected to have small volumes than the pituitary micro adenomas or craniopharyngiomas. There is no great difference in volume between the craniopharyngiomas and the pituitary macro adenomas.
The pituitary adenomas are known to result to the compression of the optic chiasm. Therefore, the evidence of compression of the optic chiasm will be a sign of the pituitary adenomas. The craniopharyngiomas will be evidenced by the occurrence of the compression of the third ventricle. The pituitary adenomas can be observed by the occurrence sellar floor depression that is more common in them than in the Rathke cleft cyst and the craniopharyngiomas. Previous research has shown that the pituitary adenomas are usually of the solid type while the craniopharyngiomas have mixed characteristics. The Rathke cleft cysts have a cystic appearance. The findings are very important in this study because they can be used to evaluate the accuracy of the findings of this study. The previous research findings have shown that there is a strong statistical difference between the frequencies of the various enhancement patterns with the pituitary adenomas and the craniopharyngiomas having the strongest frequencies (p<0.001). The enhancement patterns of the cystic regions of the three tumors will be expected to be different. The Rathke cleft cyst wall shows a thin enhancement pattern or lack of the enhancement pattern, and there exists a significant statistical difference between the cyst wall enhancement patterns of the pituitary adenomas and the other tumors. The tumor characteristics and the enhancement patterns of the cyst walls and the enhancement patterns will be used to differentiate between the three tumors in the Magnetic Resonance Imaging techniques. The techniques have been used in numerous proved researches to successfully differentiate between the three tumors.
Previous researches have shown that it is possible to distinguish between the tumors from the pituitary gland based on the intensity of the signals that are given by the tumors. In the previous studies, it was possible to visualize the cavernous sinuses in the coronal dynamic studies. It is also possible to identify the meningiomas using the MRI techniques. The identification of the sarcoma, carcinoma and the giant cell tumors has been clearer on the plain than in the delayed or the dynamic studies. The results of the study will be expected to show greater intensity of the pituitary gland than the adjacent meningiomas.
Discussion
The differential diagnosis of the craniopharyngioma, Rathke cleft cysts and pituitary adenomas that involve the intrasellar and the suprasellar regions is faced with a lot of challenges in the clinical settings. The challenges occur because many patients who suffer from these conditions present with other non specific features such as hypopituitarism, headaches and visual disturbances. The features make it difficult for the medical expert to determine immediately the condition that the patient is suffering from. The problem of diagnosing these conditions in the clinical settings is dealt with using the MRI diagnosis because the findings of these diagnoses are easy for the neurologist to interpret. Therefore, if the patient presents with the mixed disease features and the neurologist or medical physician is not sure whether the patient suffers from any of the three tumors, it is important to confirm using the MRI findings before providing medication to the patient (Suzuki et al., 2005). The unique characteristics of the three tumors in the MRI findings make it easy for the neurologist to conduct differential diagnoses of the tumors. The pituitary adenomas that extend to the suprasellar region usually have the figure eight or the snowman appearance, and they are enhanced the most among the three tumors. The features of the squamous-papillary craniopharyngioma include the presence of a solid or mixed solid or a spherical cystic tumor that is located in the suprasellar region. The tumor region is enhanced intensely and has small necrotic areas. The other features that distinguish the three tumors in the MRI are discussed in the literature (Kuperman, 2000). The neurosurgeon cannot confuse the tumors easily because of the presence of these unique features. Some image findings are more frequent in some tumors than in others. The shapes of the tumors can also be used to differentiate between the tumors as described in the literature. There are many neoplasms that appear in the region surrounding the pituitary gland such as the meningiomas, craniopharyngiomas, optic glioma, germinoma and the cavernous hemangioma (Suzuki et al., 2005). The large pituitary adenomas that extend to the para and the suprasellar regions are difficult to differentiate from the other types of tumors. There are many reports on the dynamic MR imaging of the neoplasms. According to the reports, the meningiomas have a tendency to show an early enhancement. On the other hand, the neurinomas show a gradual enhancement. In the case of the pituitary adenomas, the peak-time of the greatest enhancement of the tumor takes place later than that of the normal pituitary gland. The early enhancement of the tumor that is before the anterior lobe can be detected in the study with the use of the high temporal resolution. The vascularity of the tumors can be evaluated using the dynamic study. The previous studies have shown that the meningiomas show different enhancements in the Magnetic Resonance Imaging. The dynamic MR imaging can also be used to evaluate the non-neoplastic lesions of the parasellar region. The studies show the importance the MRI in diagnosing the pituitary disorders. The snowman characteristics of the pituitary adenoma and its appearance after the use of a contrast medium are shown in the figure 1 (a) and (b) below. The features of craniopharyngioma are shown in figure 2 (solid characteristics)
figure1. (a) shows the sagittal T1 weighted MRI image that is non enhanced. The image shows a snowman feature that is isointense in the pituitary adenoma. Image (b) shows a coronal t1weighted image that result after the administration of a contrast medium. The image shows a homogeneously enhanced pituitary adenoma that has an optic chiasm compression. Image retrieved from http://emedicine.medscape.com/article/1899167-overview#a2

Figure 2 shows the appearance of craniopharyngioma with a predominant solid characteristic. Image retrieved from http://emedicine.medscape.com/article/1899167-overview#a2

Conclusion
The studies have shown that it is possible to successfully use the magnetic resonance imaging techniques to diagnose various pituitary disorders that cannot be easily diagnosed using oter methods such as the use of the computerized tomography techniques. The most common disorders of the pituitary gland are the pituitary tumors that include the pituitary adenomas, craniopharyngiomas, and the Rathke cleft cysts. The MRI can also be used to diagnose various lesions that occur in the regions that are adjacent o the pituitary gland. The tumors are dangerous because they can be life-threatening in some cases where they affect the normal functioning of the pituitary gland. The tumors can also be dangerous if they have a malignant transformation because they can extend to other regions and cause the compression of the surrounding structures. The research has shown that it is possible to differentiate between three tumors that include the craniopharyngiomas, pituitary adenomas, and the Rathke cleft cysts involving the intrasellar and the suprasellar regions using the magnetic resonance imaging techniques. The three tumors are differentiated because of the differences in the features they show in the magnetic resonance imaging. The features are unique to each of the tumors and they include the differences in shapes, solid, semisolid or cystic appearance, and the differences in volumes of the here tumors. The enhancement patterns between the tumors are also used to distinguish between the tumors. The pituitary adenomas are usually recognized by the appearance of the figure eight or snowman appearance in the MRI images. The tumors are also recognized by the stronger enhancement among the three tumors. The squamous-papillary craniopharyngioma is distinguished because its existence in the suprasellar regions as solid, semisolid or cystic tumor that is spherical in shape. The adamantinous craniopharyngiomas are identified because of their appearance as cystic or cystic lobulate tumors that are found in the intrasellar or the suprasellar regions. The Rathke cleft cysts are recognized because of their appearance in the MRI as having a sellar epicenter, lack of calcification, having a smooth contour, lacking the internal enhancement, and having the homogeneous signal intensity in a lesion. The tumors have certain regions where they arise, and this feature is widely used to distinguish between the tumors. The pituitary adenomas mostly arise from the pituitary gland, and then develop to the diaphragm sella, and to the optic chiasm. Many cranioopharyngiomas develop from the suprasellar region, and then develop to the third ventricle, and then develop in the intrasellar region. The Rathke cleft cysts develop from the pituitary fossa, and they have small volumes because they have small extents. A lateral extent that goes beyond the ICA lateral wall is a clear indication that the patient is not suffering from the Rathke cleft cysts. The studies have revealed the importance of the enhancement patterns, and the different characteristics of the tumors in the differentiation of the three tumors. The study has also revealed the importance of the dynamic MRI in detecting the presence of the lesions that form adjacent to the pituitary gland. The dynamic MRI that is contrast enhanced has succeeded in detecting the lesions, and the meningiomas that occur adjacent to the pituitary gland. The different capacities of the meningiomas and the neurinomas to show early or gradual enhancement can be used to distinguish between the two conditions. The study has also shown the importance of the contrast enhanced MRI techniques to improve the differentiation and the visualization of the pituitary tumors. Many tumors are not visible without the contrast enhancement using media such as the gadolinium pentetate. The contrast enhanced MRI imaging allows the selective enhancement of the tumors and the surrounding tissues, making the tumors to be visible in the MRI imaging. The contrast media improve the detection accuracy in the region of 5 to 10%. The doses that are used in contrast media should be optimum because the use of too much dose can lead to the excessive enhancement of the surrounding tissues making it difficult or nearly impossible to detect the tumors. The visualization of the pituitary tumors requires the use of high resolution in order to detect the tumors. The high resolution is required because the tumors are usually very small in volume. The pituitary tumors are mainly of two types that include the tumors that produce secretions and the tumors that are not clinically functional. Many of the clinically non functional tumors do not require much medical attention because the patient can live with them if they do not lead to other symptoms that may result from extension of the tumors. The secreting tumors include the prolactin secreting tumors in women, the tumors that secret the adrenocorticotropic hormone, tumors that secret the thyroid-stimulating hormones, and the tumors that secret the growth hormones. The prolactin secreting tumors that affect women are the most common tumors, and they account for about 30 to 35% of the adenomas (de Rotte et al., 2014). The tumors are easily recognizable with the use of the magnetic resonance imaging techniques. The use of the magnetic resonance imaging is not always accurate in the recognition of the tumors because in some cases tumors are not detected. Different studies have revealed that the magnetic resonance imaging techniques are only able to detect about half of the ACTH-secreting tumors. Therefore, more research needs to be done with higher resolution and different contrast media to determine whether more tumors can be detected in the future. The clinical detection of the tumors becomes challenging in case the patient presents with mixed disease features such as visual impairment, and headache among others. The magnetic resonance imaging is used in such situations to confirm the presence of the pituitary adenomas. The information that is obtained from the findings of the MRI techniques is used by the medical physicians to make the required decisions about the medication of the patient. The findings are also used to determine whether the patient will undergo through the surgical process or receive the radiological treatment. The ultra high field strength of 7.0T can be used to image the pituitary gland in the high spatial resolution (de Rotte et al., 2014). At this field strength, the lesions that cannot be detected using the 1.5T MRI pituitary images can be detected.

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