Pituitary Macroadenoma – Evaluation of Mean Metabolic Ratios and Mean and Normalized Apparent Diffusion Coefficient Values Using Magnetic Resonance Spectroscopy and Diffusion-weighted Imaging in a Central Indian Rural Hospital Setup

Gaurav Vedprakash Mishra; K B Harshith Gowda; Pratik J Bhansali; Vadlamudi Nagendra; Nishant Raj

doi:10.4103/jdmimsu.jdmimsu_565_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 17 | Issue : 4 | Page : 838-841

Pituitary Macroadenoma – Evaluation of Mean Metabolic Ratios and Mean and Normalized Apparent Diffusion Coefficient Values Using Magnetic Resonance Spectroscopy and Diffusion-weighted Imaging in a Central Indian Rural Hospital Setup

Gaurav Vedprakash Mishra, K B Harshith Gowda, Pratik J Bhansali, Vadlamudi Nagendra, Nishant Raj
Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra, India

Date of Submission	18-Nov-2022
Date of Acceptance	19-Nov-2022
Date of Web Publication	10-Feb-2023

Correspondence Address:
Dr. Gaurav Vedprakash Mishra
Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jdmimsu.jdmimsu_565_22

Abstract

Background: MRS and disregard MRI spectroscopy offers the capability of using magnetic resonance imaning (MRI) to noninvasively study tissue biochemistry. MRS is noninvasive technique that is used to study metabolic variance in brain tumors. Furthermore, diffusion-weighted imaging depicts the degree of water molecules diffusing across the unit volume of the region of interest as a result of sophisticated and dedicated software packages. Differences in apparent diffusion coefficient (ADC) values are related to changes in cellularity, cell membrane permeability, intracellular and extracellular diffusion, and tissue structure. Diffusion-weighted MRI is a powerful tool in the characterization of brain neoplasms. The present study attempts to derive the mean metabolite ratios as well as mean values of ADC with normalization in the setting of pituitary macroadenoma. Aim: (1) To evaluate mean metabolic ratios in pituitary macroadenomas using magnetic resonance spectroscopy (MRS) in rural hospital setup in Central India, (2) To evaluate mean apparent diffusion coefficient value with normalization in pituitary macroadenoma using magnetic resonance spectroscopy in a rural hospital setup in Central India. Materials and Methods: A cross-sectional hospital-based observational study conducted over 2 years. All cases registered with Acharya Vinoba Bhave Rural Hospital Sawangi, Wardha, diagnosed as pituitary macroadenomas were included in the present study. All patients were examined on GE Brivo MRI machine with 1.5 Tesla magnetic field strength in the Department of Radiodiagnosis. Diagnostic acumen was augmented with radiological features of brain tumors with metabolic ratios derived from metabolic values and ADC values. Results: Out of 142 patients included, pituitary macroadenoma cases were 18 in number. Observed metabolite ratios were derived from metabolic values obtained on MRS for choline (Cho), creatinine (Cr), lipid lactate, myoinositol, and n-acetyl aspartate (NAA). Ratios were calculated for Cho: Cr, Cho: NAA, Cho: myoinositol and Cho: lipid lactate. The range for Cho: Cr, Cho: NAA, Cho: myoinositol, and Cho: lipid lactate was 1.04–4.73, 0.96–4.12, 1.21–3.12, and 0.72–1.812, respectively. The mean values for Cho: Cr, Cho: NAA, Cho: myoinositol, and Cho: lipid lactate were 1.8655, 1.6094, 1.5561, and 1.4567, respectively. The range of ADC values observed was from 0.821 × 10⁻³ mm²/s to 1.523 × 10⁻³ mm²/s. Normalized ADC values were calculated on basis of observed ADC values in the numerator and the average ADC value of gray matter in the denominator which is taken as 0.8 and was in the range of 1.02625 × 10⁻³ mm²/s to 1.90375 × 10⁻³ mm²/s. The mean ADC value was calculated as 1.22 × 10⁻³ mm²/s. The mean normalized ADC value was calculated as 1.52 × 10⁻³ mm²/s. Conclusion: The research gap analysis toward which research question was framed stands filled up by generated new knowledge in terms of “mean metabolic ratios” and “ADC” values with reference to pituitary macroadenomas in the present study.

Keywords: Apparent diffusion coefficient, magnetic resonance spectroscopy, mean metabolic ratios, pituitary macroadenoma

How to cite this article:
Mishra GV, Gowda K B, Bhansali PJ, Nagendra V, Raj N. Pituitary Macroadenoma – Evaluation of Mean Metabolic Ratios and Mean and Normalized Apparent Diffusion Coefficient Values Using Magnetic Resonance Spectroscopy and Diffusion-weighted Imaging in a Central Indian Rural Hospital Setup. J Datta Meghe Inst Med Sci Univ 2022;17:838-41

How to cite this URL:
Mishra GV, Gowda K B, Bhansali PJ, Nagendra V, Raj N. Pituitary Macroadenoma – Evaluation of Mean Metabolic Ratios and Mean and Normalized Apparent Diffusion Coefficient Values Using Magnetic Resonance Spectroscopy and Diffusion-weighted Imaging in a Central Indian Rural Hospital Setup. J Datta Meghe Inst Med Sci Univ [serial online] 2022 [cited 2023 Apr 1];17:838-41. Available from: http://www.journaldmims.com/text.asp?2022/17/4/838/369514

Introduction

Magnetic resonance imaging spectroscopy (MRS) enhances the innate ability to study the biochemical details of a particular tissue in question in a noninvasive manner. A voxel is the volumetric representation of the said tissue in a box within which a given region can be studied and information on the biochemical substance molecules is usually presented as a spectrum. The precession frequency on the horizontal axis representing the identity of a biochemical compound and its intensity on the vertical axis thus assisting in quantifying the concentration of a particular compound within the region of interest of the tissue. Thus, it can be employed to get a glimpse of any regional biochemical alterations or abnormalities with the specialized function to create a graphical representation having four main metabolites related to brain tumors, i.e., n-acetyl aspartate (NAA), Cr, choline (Cho), and creatinine (Cr).^[1]

It is a very particular method that enables recognition of particular metabolites in samples of interest and the ones in question differing from conventional magnetic resonance imaging (MRI) where spectra provide physiological and chemical information instead of anatomical revelation. These may be acquired or derived from multiple nuclei but protons or simply hydrogen is the most used for such applications in the human brain mainly due to its higher sensitivity and at the same time, abundance.^[2]

One of the most common tumors of the sellar region is pituitary macroadenoma.^[3] Diagnosing them has been eased out by the advent of MRI as an imaging modality by the use of specialized imaging sequences, namely, diffusion-weighted imaging (DWI). The degree of water molecules diffusing across the unit volume of the region of interest can be depicted as a number as a result of sophisticated and dedicated software packages. These differences in apparent diffusion coefficient (ADC) values are reflective of alteration in cellularity, permeability of cell membranes, diffusion occurring at intracellular and extracellular aspects of the cells, and overall tissue structure as well thus playing a vital role in the characterization of brain neoplasms. Cellularity within tumors and tumor grades have been statistically correlated previously with ADC values as well.

The present study attempts to derive the mean metabolite ratios as well as mean ADC values with normalization in the setting of pituitary macroadenoma.

Materials and Methods

Study design and setting

The present study is a cross-sectional prospective observational study.

All patients in the present study were examined on the GE Brivo MRI machine with 1.5 Tesla magnetic field strength in the Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha.

All the patients had given written informed consent after having read and understood the information which was provided regarding the study being conducted and had the opportunity to ask their own questions or doubts if any, regarding benefits or risks involving the same and that their participation being voluntary, they were free to withdraw without giving reason whatsoever and without cost anytime.

Institutional Ethics Committee Clearance with reference number DMIMS (DU)/IEC/2015-16/1971 depicts the ethical clearance obtained to conduct the present study.

Study period

This study was conducted for two years – April 12, 2016–April 11, 2018.

Participants

All patients registered with Acharya Vinoba Bhave Rural Hospital, Jawaharlal Nehru Medical College, Sawangi, Wardha, diagnosed with pituitary macroadenomas, meningeal tumors, and tumors of the Sellar region were included in the present study.

Tumour group studied in the present study

Pituitary macroadenomas.

Inclusion criteria

All patients aged 4 years and above are histopathologically diagnosed with pituitary macroadenomas
All patients with MRI data of satisfactory imaging quality for the purpose of correlation
Those giving informed consent.

Exclusion criteria

Patients aged <4 years of age (MR spectra of metabolites are difficult to distinguish between due to rapid metabolic changes until the age of 4 years of age)
Patients with poor quality MRI data – due to artifacts or contamination by the unwanted metabolites or magnetic in homogeneities
Patients with pacemakers
Patients with cochlear implants
Patients with claustrophobia
Patients not agreeing to give informed consent.

Results

In the present study, the total number of cases included was 142 which included pituitary macroadenomas, meningeal tumors, and sellar tumors. Out of these, there were 18 cases diagnosed radiologically and histopathologically as pituitary macroadenomas. In the present study, out of the total of 142 patients included, the pituitary macroadenomas cases were 18 in number. The observed metabolite ratios in the present study were derived from the metabolic values obtained on MRS for Cho, Cr, lipid lactate, myoinositol, and NAA. The ratios were calculated for Cho to Cr, Cho to NAA, Cho to myoinositol, and Cho to lipid lactate. The range for Cho to Cr, Cho to NAA, Cho to myoinositol, and Cho to lipid lactate was 1.04–4.73, 0.96–4.12, 1.21–3.12, and 0.72–1.812, respectively. The mean values for Cho: Cr, Cho: NAA, Cho: myoinositol, and Cho: lipid lactate were 1.8655, 1.6094, 1.5561, and 1.4567, respectively.

Values were obtained for all cases and were subjected to normalization by taking the observed value in the numerator and taking the normal average ADC of normal gray matter as 0.8 in the denominator. The values so obtained were called normalized ADC values and are depicted in [Table 1]. The range of ADC values observed was observed to be from 0.821 × 10⁻³ mm²/s to 1.523 × 10⁻³ mm²/s. The normalized ADC values were calculated based on observed ADC values and were in the range of 1.02625 × 10⁻³ mm²/s to 1.90375 × 10⁻³ mm²/s. The mean ADC value was calculated to be 1.22 × 10⁻³ mm²/s. The mean normalized ADC value was calculated to be 1.52 × 10⁻³ mm²/s. The results are tabulated as in [Table 1], [Table 2], [Table 3] systematically.

Table 1: Observed values for metabolite ratios with respective mean values

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Table 2: Observed values for apparent diffusion coefficient and normalized values with respective mean values

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Table 3: Observed values for apparent diffusion coefficient and normalized values with respective mean values by other study groups

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Discussion

Mohammad et al.^[4] in 2014, studied 30 cases of suprasellar space-occupying lesions, and MRS findings were correlated. On MRS, macroadenoma showed significant reduction in NAA with moderate Cho elevation, Cr reduction, and commonly observed small lipid/lactate peaks.

Stadlbauer et al.^[5] in 2008 evaluated 37 pituitary macroadenoma cases on a 1.5-T unit. The Cho concentration ranged from 1.8 to 5.2 and 11 cases showed hemorrhagic transformation within the adenoma with no observable Cho concentration.

Studies in literature have shown a variable trend with regard to metabolite concentrations of Cho, NAA, and lipid lactate. The main roles of these metabolites are cellularity and turnover for Cho, overall neuronal health and integrity for NAA and cell membrane lysis for lipid lactate.^[2],[6] Increased level of Cho can represent also an increased function of pituitary cells with regard to their endocrine regulatory roles. Therefore, a spectrum of signs and symptoms can be observed in such cases as a result of higher concentrations of characteristic hormones produced by the adenohypophysis or the neurohypophysis of the pituitary gland situated in the sella turcica. Proper attention needs to be paid to such signs and symptoms when they present, and MRI investigation coupled with MRS imaging sequence will always be of use as it will reflect the cellular metabolic picture accurately if the voxels are placed suitably within the tumoral mass.

In the present study, out of the total of 142 patients included, the pituitary macroadenomas cases were 18 in number. The observed metabolite ratios in the present study were derived from the metabolic values obtained on MRS for Cho, Cr, Lipid lactate, myoinositol, and NAA. The ratios were calculated for Cho: Cr, Cho: NAA, Cho: myoinositol, and Cho: lipid lactate. The range for Cho: Cr, Cho: NAA, Cho: myoinositol, and Cho: lipid lactate was 1.04–4.73, 0.96–4.12, 1.21–3.12, and 0.72–1.812, respectively. The mean values for Cho: Cr, Cho: NAA, Cho: myoinositol, and Cho: lipid lactate were 1.8655, 1.6094, 1.5561, and 1.4567, respectively.

These findings are similar to those reported by Mohammad et al.^[4] and Stadlbauer et al.^[5] and suggest MRS investigation as an adjunct supporting pillar for diagnosing sellar masses and depicting cellular metabolic without surgically invading the patient, thus providing ample opportunity for the surgeon to plan his approach and extent of surgery beforehand.

The range of ADC values observed was 0.821 × 10⁻³ mm²/s to 1.523 × 10⁻³ mm²/s. The normalized ADC values were in the range of 1.02625 × 10⁻³ mm²/s to 1.90375 × 10⁻³ mm²/s. The mean ADC value was 1.22 × 10⁻³ mm²/s and the mean normalized ADC value was 1.52 × 10⁻³ mm²/s.

Mohammad et al.^[7] in 2014, studied 30 suprasellar space-occupying lesions and attempted to correlate their findings. On MRS, macroadenoma revealed a significant reduction in NAA levels, moderate Cho elevation, reduced Cr, and frequent small lipid/lactate peaks showing mean ADC value of 0.6 × 10⁻³ mm²/s.

They examined 30 cases with pituitary adenomas by DWI with ADC value measurement. They grouped their cases into three groups of macroadenoma based on the tumor consistency: Group A with mean ADC value of 0.482 × 10⁻³ mm²/s naming them as soft adenomas (22 out of 30), Group B having a mean ADC value of 0.730 × 10⁻³ mm²/s calling them adenomas with intermediate consistency (5 out of 30), and Group C with mean ADC value of 0.992 × 10⁻³ mm²/s terming them as firm adenomas (3 out of 30).

The present study reports findings in consonance with the study groups mentioned above.

Conclusion

In the present study, the individual and mean metabolite ratios were calculated on MRS. The research gap analysis toward which research question was framed stands filled up by the generated new knowledge in terms of “Mean Metabolite ratios” in the setting of cerebral pituitary macroadenomas cases in a rural hospital setup in Central India. A perspective of intracellular metabolic pictures within the tumoral tissue being deciphered using advanced technology without invasion of the patient's body can be considered the essence of the present study.

The main conclusion can be safely stated that the lower the grade of the tumor, the more the value of the ADC and normalized ADC for a given unit volume of tumoral mass. Pituitary macroadenomas are grade 1 tumors and are benign with minimal cell destruction, nuclear atypia, or degenerative signs on a microscopic level.^[8] Thereby the degree of diffusion of water molecules across a given unit of volume of the region of interest may not get deviated in a significant manner.

“Cutoff” values have been calculated by means of the application of logistic regression analysis and region operating characteristic curves therein.^[9],[10] The same can be applied to the present study as a suggested future outcome and is advisable and more fruitful to conduct a study of similar nature at multiple centers simultaneously to have a better representative sample size and multiple demographic details involved therein.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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