Mean and normalized apparent diffusion coefficient values and mean metabolic ratios in cerebral metastases in central Indian rural hospital setup

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

doi:10.4103/jdmimsu.jdmimsu_567_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 17 | Issue : 4 | Page : 842-846

Mean and normalized apparent diffusion coefficient values and mean metabolic ratios in cerebral metastases in central Indian rural hospital setup

Gaurav Vedprakash Mishra, Harshith Gowda, Pratik Bhansali, Nagendra Vadlamudi, 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	19-Nov-2022
Date of Decision	20-Nov-2022
Date of Acceptance	21-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_567_22

Abstract

Background: To evaluate mean metabolite ratios and Apparent diffusion co-efficient value with normalization in cerebral metastases using MRS in rural hospital setup in Central India. Method: A cross sectional hospital based observational study conducted over a time period of 2 years. All the cases registered with Acharya Vinoba Bhave Rural Hospital ,Sawangi, Wardha, diagnosed on histopathological findings as cerebral metastases were included in this present study. All patients were examined on GE Brivo MRI machine with 1.5Tesla magnetic field strength in the Department of Radiodiagnosis using b value of 1000 s/sq. mm, slice thickness 5mm, interslice gap 2mm applied in the x, y and z axes, central as well as peripheral portions of the tumor were manually sampled, preferably getting rid of cystic or necrotic areas. Histopathological diagnostic acumen was augmented with ADC values with normalization. Result: Range of ADC values observed was from 0.683 10-3 mm2/s to 0.873 10-3 mm2/s. Normalized ADC values were calculated on basis of observed ADC values and were in range of 0.8537510-3 mm2/s to 1.09125 10-3 mm2/s. Mean ADC value was calculated as 0.749 x 10-3 mm2/s. Mean normalised ADC value was calculated to be 0.9372 x 10-3 mm2/s. Observed metabolite ratios were derived from metabolic values obtained on MRS for Choline, Creatinine, Lipid lactate, myoinositol and n-acetyl aspartate. Range for Choline:Creatinine, Choline:n-acetyl aspartate, choline : myoinositol and choline : lipid lactate was 3.97 to 5.73, 3.24 to 5.76, 4.35 to 5.49 and 0.32 to 0.997 respectively. Mean values for Choline:Creatinine, Choline:n-acetyl aspartate, choline : myoinositol and choline : lipid lactate were 4.1289, 3.7838, 4.1256 and 0.9095 respectively. Conclusion: Research gap analysis towards which research question was framed stands filled up by the generated new knowledge in terms of 'Mean metabolite ratios','Apparent Diffusion Coefficient' and 'Normalised Apparent Diffusion Coefficient' values for cerebral metastases in the present study.

Keywords: Apparent diffusion coefficient, metabolite ratio, metastasis, normalized apparent diffusion coefficient

How to cite this article:
Mishra GV, Gowda H, Bhansali P, Vadlamudi N, Raj N. Mean and normalized apparent diffusion coefficient values and mean metabolic ratios in cerebral metastases in central Indian rural hospital setup. J Datta Meghe Inst Med Sci Univ 2022;17:842-6

How to cite this URL:
Mishra GV, Gowda H, Bhansali P, Vadlamudi N, Raj N. Mean and normalized apparent diffusion coefficient values and mean metabolic ratios in cerebral metastases in central Indian rural hospital setup. J Datta Meghe Inst Med Sci Univ [serial online] 2022 [cited 2023 Apr 1];17:842-6. Available from: http://www.journaldmims.com/text.asp?2022/17/4/842/369515

Introduction

In the nations with a developing status, health and healthcare services have been a matter of neglect. Many health disorders arise and become harder to conquer and cure, more so to prevent and protect against. The recent pandemic of COVID-19 is a classic example of the same. It hit the entire globe and literally devoured it on all grounds – economy, health, infrastructure, and international trade. The entities which come under the class of diseases and disorders are innumerable, and therefore, mankind is forced to produce protective measures which are generic and specific for the said threat to protect themselves from its negative effects. Talking about tumors, the most feared ones are malignant and are subdivided by World Health Organization into Grade 3 and Grade 4, respectively of which those tumors which have an innate tendency to spread and migrate from their primary site through blood, lymph, or contact are known as “metastases.”^[1]

The modalities invented for diagnosing these include radiological ones such as computed tomography, magnetic resonance imaging (MRI), and multiple imaging sequences within it. One of the interesting and useful techniques under MRI is diffusion-weighted imaging where the degree of diffusion of water molecules across a tissue can be calculated by specialized software and a value is derived mathematically which denotes the same – called as “apparent diffusion coefficient” value.

Magnetic resonance spectroscopy (MRS) has made several breakthroughs recently has become an irreplaceable tool to study in vivo biochemical aspects of disorders of the brain and various other organs of the human body. Since almost all metabolites contain hydrogen atoms, investigation by in vivo MRS incorporating hydrogen ions provides chemical data and crucial information on biological metabolites thus empowering the noninvasive nature of assessment of any alteration in brain metabolism underlying several brain diseases.^[2]

Hydrogen (H1), phosphorus (P31), carbon 13 (C13), fluorine 19 (F19), and sodium 23 (Na23) are various metabolite ions which can be used for deriving spectroscopic data MR spectroscopy. Concentration of hydrogen and phosphorus both these ions in the central nervous system tissue is sufficient to be useful in clinical MR spectroscopy with hydrogen being best suited for MR spectroscopy because of its high concentration, favourable relaxation time, and high gyromagnetic ratio. At the same time, Phosphorus 31 offers a relatively lower gyromagnetic ratio and concentration making it all the way less popular than hydrogen based spectroscopy. Using phosphorus 3, it is difficult to obtain sufficient signal-to-noise ratio (SNR) on a voxel size routinely used voxel size used for Hydrogen MR spectroscopy.^[3]

Chemical shift forms the core of MRS while it is the cause of artefacts in MRI. Precession frequency of protons is based upon the electron cloud surrounding the proton itself. Protons process at different frequency in different media, different for water, different for fat, and the same protons in other metabolites will precess at different frequency. This change in precession frequency because of different environment is termed chemical shift. So precession frequency determination may lead to the identification of metabolites.

Chemical shift being directly proportional to magnetic field strength (B0), chemical shift with smaller magnitudes may not be detectable at lower field strength. MRS can be performed on 0.5 Tesla or above no doubt, but a 1.5 Tesla field strength or above is desired for enhanced distinction of the metabolite spectra as well as increased SNR thereby requiring a more homogenous magnetic fields to detect metabolites with lower concentration.^[4]

The present study attempts to evaluate the mean and normalized apparent diffusion coefficient (ADC) values as well as mean metabolite ratios in patients diagnosed as cerebral metastases in a Central Indian Rural Hospital Setup in Wardha, Maharashtra, India.

Materials and Methods

Study design and setting

The present study is cross-sectional prospective observational study carried out in the Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha where all cases were examined on GE Brivo MRI machine with 1.5 Tesla magnetic field strength. All the patients had given a written informed consent after having read, 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 in order to conduct the present study.

Study period

Two years – April 12, 2016–April 11, 2018.

Participants

All cases registered with Acharya Vinoba Bhave Rural Hospital, Jawaharlal Nehru Medical College, Sawangi, Wardha, diagnosed with glial tumors, meningial tumors, and tumors of the Sellar region were included in this present study.

Tumor groups studied

Cerebral metastases (n = 13).

Sample size

The sampling technique employed for the present study was convenient purposive sampling technique. The sample size availed in the present study was 142, out of which cerebral metastases were 13.

Inclusion criteria

All patients aged 4 years and above diagnosed as cerebral metastases
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 age of 4 years of age)
Patients with poor quality MRI data – due to artefact or contamination by the unwanted metabolites or magnetic inhomogeneities
Patients with pacemakers
Patients with cochlear implants
Patients with claustrophobia.

Results

In the present study, the total number of cases included were 142 which included glial tumors, meningeal tumors, and sellar tumors. Out of these, there were 13 cases diagnosed radiologically as cerebral metastases. The ADC values were obtained for each case and were subjected to normalization by taking the observed value in the numerator and taking the average ADC of normal greay matter as 0.8 in the denominator. These values were normalized ADC values. Range of ADC values was from 0.683 × 10⁻³ mm²/s to 0.873 10⁻³ mm²/s. The normalized ADC values were calculated on the basis of observed ADC values and were in the range of 0.8537510⁻³ mm²/s to 1.09125 10⁻³ mm²/s. The mean ADC value was calculated to be 0.749 × 10⁻³ mm²/s. The mean normalized ADC value was 0.9372 × 10⁻³ mm²/s.

The observed metabolite ratios in the present study were derived from the metabolic values obtained on MRS for choline, creatinine, lipid lactate, myoinositol, and n-acetyl aspartate. The ratios were calculated for Choline to Creatinine, Choline to n-acetyl aspartate, choline to myoinositol, and choline to lipid lactate. The range for Choline to Creatinine, Choline to n-acetyl aspartate, choline to myoinositol, and choline to lipid lactate was 3.97–5.73, 3.24–5.76, 4.35–5.49, and 0.32–0.997, respectively. The mean values for Choline: Creatinine, Choline: n-acetyl aspartate, choline: Myoinositol and choline: Lipid lactate were 4.1289, 3.7838, 4.1256, and 0.9095, respectively.

The results are systematically tabulated in [Table 1], [Table 2], [Table 3], [Table 4], respectively.

Table 1: Observed values for apparent diffusion coefficient and normalised values with respective mean values

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Table 2: Observed values for apparent diffusion coefficient and normalised values with respective mean values by other study groups

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Table 3: Observed values for metabolite ratios with respective mean values

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Table 4: Observed values for metabolite ratios with respective mean values from other study groups

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Discussion

The findings in the present study in regard to ADC and nADC are in tune with the findings of Dawoud et al.,^[6] Darweesh et al.,^[5] and Bulakbasi et al.^[7] to the effect that lower ADC values were attributable to high grade tumors.

The decrease in ADC values in high grade tumors such as cerebral metastases and even others falling in the same category as grade 4 brain tumors can be attributable to certain key factors. The volume of fluid in the intracellular and extracellular space as well as the factors which are responsible in making deviations in these can be collectively held responsible for the notable shift of derived ADC values and normalized ADC values therein.

High grade tumors possess high degree of cell division and therefore correspondingly higher degree of cell death. Therefore, the number of cells in a given volume in a high-grade tumor will be comparatively higher than that of a low-grade tumor or even normal brain tissue. As the number of cells increase, the amount of fluid being a reservoir for all cells in that given volume gets distributed into many smaller intracellular and extracellular spaces making it harder for water molecules to diffuse across multiple cells through their cell membranes and thereby causes a decrease in the observed ADC value and normalized ADC value as well.

Another factor which has to be taken care of is cell necrosis – which gives erroneous values as the necrotic areas only consist of dead cells and the extracellular component being much greater leads to a higher ADC and normalized ADC value. It is for this reason that the voxel placement while obtaining these values that necrotic and degenerative areas are to be avoided.^[8]

All the cases showed high ratios of Cho/Cr, Cho/NAA levels, and Cho: mI, whereas Cho: LL was variable in concentration. These findings corroborate with the studies done Poptani et al.,^[9] Darweesh et al.,^[5] Kaddah and Kaddah,^[10] Dawoud et al.,^[6] Sherbeny et al.,^[11] and Majós et al.^[12]

The elevation of choline can be explained by the increased rate of cell reproduction and cell death within the tumoral tissue. Creatinine being the source of energy for the cells in toto will be subjected to competitive extraction by the cells overall and being limited in concentration, it will get exhausted earlier, thereby showing decreased concentration and depleted peaks on MRS. N-acetyl aspartate being a neuronal health marker will show depletion as cells within the tumoral tissue are undergoing cell destruction and correspondingly lysis of the cell membrane and intracellular components will lead to increase in the level of lipids and lactates within the tumoral tissue. Myoinositol will also follow the same trend as creatinine and n-acetyl aspartate. Other studies have studied different tumor classes such as low grade gliomas, high grade gliomas and have inferred individual, mean as well as 'cutoff' values by means of suitable statistical analyses.^[13],[14]

Conclusion

Out of the total of 142 patients included, the cerebral metastases cases were 13. The range of ADC values observed was from 0.683 10^{− 3} mm²/s to 0.873 10^{− 3} mm²/s. The normalized ADC values were calculated on the basis of observed ADC values and were in the range of 0.8537510^{− 3} mm²/s to 1.09125 10^{− 3} mm²/s. The mean ADC value was calculated to be 0.749 × 10^{− 3} mm²/s. The mean normalized ADC value was calculated to be 0.9372 × 10^{− 3} mm²/s. Thus, it can be concluded through the present study that the higher the degree of the tumor, the more malignant it is by nature and less is the degree of diffusion of water molecules across the cell membranes within a given volume of tumour cells.

In the present study, the individual and mean metabolite ratios were calculated and the research gap analysis stands filled up by the generated new knowledge in terms of “Mean Metabolite ratios” in the setting of cerebral metastases cases in a rural hospital setup in Central India. A perspective of intracellular metabolic picture 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. “Cutoff” values for demarcation of high-grade and low-grade tumors have been carried out making the use of logistic regression analysis and receiver operating characteristic curves.^[13],[14] Similar studies need to be carried out on a multicentric multinational basis to have a more representative sample size of the population for obtaining stronger and more generalized results – making this a potential future study objective for the present study as well.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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