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MRI Scan for Pulmonary Embolism: A Meta-Analysis

Title:Diagnostic performance of magnetic resonance imaging for pulmonary embolism: a meta-analysis
Highlights:
This study was performed to analyze the diagnostic performance of MRI for PE.
High sensitivity and specificity of MRI diagnosis for PE was proved.
MRI diagnosis had low missed diagnosis and misdiagnosis rates in detecting PE.
MRI had strong discriminative ability for confirming PE.
Good diagnostic performance of MRI for PE was proved.
Abstract
Objective: The aim of this meta-analysis was to analyze the diagnostic performance of magnetic resonance imaging (MRI) for pulmonary embolism (PE).
Methods: A systematic literature search was conducted up to November 2013 by using the electronic databases and paper literatures. The 14-item quality assessment of diagnostic accuracy studies (QUADAS) list was used to evaluate the quality of the studies. Meta-disc software version 1.4 was used to analyze the data. CT was used as “gold standard”.
Results: Finally, 5 eligible literatures were included in this meta-analysis. Sensitivity in each study ranged from 78% to 100% and specificity ranged from 99% to 100%. The pooled estimate of sensitivity (83%, 95%CI: 78%-88%) and specificity (99%, 95%CI: 98%-100%) demonstrated that MRI diagnosis had high sensitivity and specificity in the detection of PE. The pooled estimate of positive likelihood ratios (PLR) (70.22, 95%CI: 29.04-169.76) and negative likelihood ratios (NLR) (0.19, 95%CI: 0.14-0.25) provided evidence for low missed diagnosis and misdiagnosis rates of MRI diagnosis for PE. The strong discriminative ability of MRI for confirming PE was proved by the overall diagnostic odds ratio (DOR) (448.98, 95%CI: 163.47-1233.18) and the summary receiver operating characteristic (SROC) curves (AUC=0.9852±0.0052) demonstrated the superior diagnostic performance of MRI.
Conclusions: In conclusion, MRI is a diagnostic method of PE with the good diagnostic performance of high sensitivity and specificity, low missed diagnosis and misdiagnosis rates and strong discriminative ability.
Keywords: magnetic resonance imaging, diagnosis, pulmonary embolism, meta-analysis
Introduction Pulmonary embolism (PE) is a common complication of deep vein thrombosis [1]. As a potentially fatal disorder [2], PE usually lead to death after right ventricular (RV) failure and circulatory collapse [3]. Early mortality for PE ranged from 5% in patients with stable clinical conditions to 58% in patients with cardiogenic shock [4]. At present, this mortality was still high. An recent study [5] published in 2013 reported that the mortality for PE was up to 67% in the patients with persistent hyponatremia. An accurate diagnosis of PE is the basis of the prevention and treatment of PE. However, missed diagnosis and misdiagnosis of PE is common in current clinical practice. Thus, to find the diagnostic methods with superior diagnostic performanceis an imperative study now.
With the development of the science and technology, more and more diagnostic methods are used to diagnosing PE. Such as electrocardiography (ECG) [6], chest X-ray[7], computed tomography (CT) [8] and magnetic resonance imaging (MRI) [9], they are all commonly used in the clinical diagnosis of PE. In the early 90s, The advent of spiral CT technology was aiming to change the diagnostic capability of PE [10]. Currently, CT is one of the most reliable and effective diagnostic methods for PE [11] and has been used as a “gold standard” [12]. MRI is an established imaging modality in thoracic diseases [13] and ongoing technical developments have substantially improved the capability of MRI in the diagnosis for PE [14]. However, there was no enough evidence to validate MRI as an alternative diagnostic method to CT in patients with clinically suspected PE [15]. Therefore, we performed a meta-analysis to verify the good diagnostic performance of MRI for PE with CT as the “gold standard”.
Methods Search strategy
A systematic literature search was conducted up to November 2013 by using the electronic databases such as PubMed, Embase and Springer link. The keywords included “Pulmonary Embolism” and “MR imaging” or “MR” or “MRI” or “Magnetic Resonance Imaging” or “Magnetic Resonance”. Furthermore, paper literatures were retrieved by manual search. Review articles and reference lists of retrieved articles were also inspected to find additional eligible studies.
Study selection
After the initial search, we imposed additional criteria as follows: (1) the trials involved MRI diagnosis for PE; (2) the subjects were the patients with suspected PE and beyond 18 years of age; (3) CT was used as the “gold standard”; (4) the data of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) were contained or could obtain by calculation.
Studies were excluded if one of the following existed: (1) MRI examination was not conducted in 48h after CT examination, (2) the language of the study was not English, and (3) the literatures were reviews, letters and comments.
Data extraction and quality assessment
Two investigators independently extracted the data from all eligible studies according to the criteria listed above. Disagreements were resolved by discussion. The following information was extracted: the first author name, year of publication, region, age and gender of subjects, sample size, data of TP, FP, TN and FN, magnetic field intensity and MRI scan sequence.
We used 14-item quality assessment of diagnostic accuracy studies (QUADAS) list [16] to evaluate the quality of the studies. Due to the association of quality assessment with the description of the method and result in the literatures, low score was often obtained when the details of them were not reported. Thus, we used“yes”, “no” and “not clear” as assessment standards rather than scores.
Statistical analysis
In this meta-analysis, Meta-disc software version 1.4 [17]was used to analyze the data. Summary receiver operating characteristic (SROC) curve, sensitivity(Sen), specificity (Spe), positive likelihood ratios (PLR), negative likelihood ratios (NLR), diagnostic odds ratio (DOR) as well as their 95% confidence interval (CIs) were calculated to evaluate the diagnostic performance of MRI for PE. The higher the DOR, the stronger the diagnostic power of MRI in the detection of PE [18]. The analysis of SROC curves was based on the data of Sen and Spe. The area under the curve (AUC) was used to quantitatively measure the performance of MRI. Superior diagnostic performance is proved if the AUC is close to 1 [19]. Cochran’s Q and I2 statistics (I2>50%) was used to test the heterogeneity of the pooled data of DOR, PLR and NLR. The heterogeneity of the pooled data of Sen and Spe were evaluated by using chi-square test and I2 statistics (I2>50%). Threshold effect (p<0.05) was evaluated by spearman correlation analysis [20].
Results Literature search
After initial literature search and removing the duplicated articles, there were 1748 potential relevant literatures was remained. Among them, 1714 irrelevant articles were excluded by scanning the titles and abstracts. Among the remaining 34 literatures, 29 articles were removed. They included 7 reviews, 5 conferences, 4 non-English articles, 2 comments and 11 articles without involving PE. After removing them, 5 eligible literatures [21-25] were included to do this meta-analysis.
Characteristic of included studies
The 5 included studies were published from 2006 to 2013. A total of 679 subjects aged from 18 to 82 were included. The studies were conducted in the regions of Germany [21], Canada [22], French [23], China [24] and USA [25]. The data of MRI scan sequence were reported in all included studies except the study of Stein et al. [25] and the gender of the subjects were also not reported in this study (Table 1).
Based on the results of quality assessment shown in Table 2, we knew that all included studies reported the content of first to 9th and 14th terms. The content of 12th terms was only reported in the study of Kluge et al. [21]. The content of 10th term was not reported in the study of Stein et al. [25] and Zhang et al. [24] and not clear in the study of Pleszewski et al. [22]. The content of 11th term was not reported in the study of Revel et al. [23] and Zhang et al. [24] and not clear in the study of Kluge et al. [21].
Performance assessment of MRI diagnosis
Forrest plots for sensitivity and specificity were shown in Fig. 2. For sensitivity, significant heterogeneity (P=0.0295, I2=62.8%) was found among the studies. Thus, the random-effects model was used to pool the data. Sensitivity in each study ranged from 78% to 100%. The pooled estimate of sensitivity was 83% (95%CI: 78%-88%). For specificity, there was no significant heterogeneity among the included studies. Thus, the data were pooled by fixed-effects model. Specificity in each study ranged from 99% to 100% and the pooled estimate was 99% (95%CI: 98%-100%). The above results demonstrated thatMRI had high sensitivity and specificity in the detection of PE.
Forrest plots for PLR and NLR were shown in Fig. 3. For PLR and NLR, no significant heterogeneity (PLR: P=0.4802, I2=0.0%; NLR: P=0.4258, I2=0.0%) was existed in the included studies. Then fixed effects model was used to pool the data. The pooled estimate of PLR (70.22, 95%CI: 29.04-169.76) and NLR (0.19, 95%CI: 0.14-0.25) provided evidence for the low missed diagnosis and misdiagnosis rates of MRI diagnosis for PE.
Forrest plot of the DOR and SROC curves were shown in Fig. 4. For DOR, no significant heterogeneity (P=0.9077, I2=0.0%) was found among the included studies. so fixed effects model was used to pool the data. The overall DOR was 448.98 (95%CI: 163.47-1233.18). It demonstrated the strong discriminatory ability of MRI in the detection of PE. The SROC curves (AUC=0.9852±0.0052) showed superior diagnostic performance of MRI and the result of spearman correlation analysis indicated that there was no threshold effect (p=0.624).
Discussion In this meta-analysis, we concluded that MRI, as a diagnostic method for PE, had the characteristics of high sensitivity and specificity. Based on the data of PLR and NLR, we knew MRI had low missed diagnosis and misdiagnosis rates in detecting PE. The overall DOR demonstrated the strong diagnostic ability of MRI diagnosis for PE. The AUC of SROC curves was close to 1 and it revealed the superior diagnostic performance of MRI.
MRI is a powerful imaging modality that provides internal images of materials and living organisms on a microscopic and macroscopic scale [26]. In MRI diagnosis, the image is constructed by magnetic resonance that is generated from the electromagnetic signals emitted by the protons of the body [27]. Compared to CT, MRI has three clear advantages. The first advantage of MRI is lack of exposure to ionizing radiation and no using of iodinated contrast media [21]. The second one is the capability of 3D-multiplanar imaging and simultaneous imaging of multiple sections [28]. Third, a variety of imaging parameters can be obtained to provide diagnostic information [29]. These advantages indicate that MRI diagnosis is reliable and safe in the detection of PE and may supplant the position of CT in future.
Some limitations of this meta-analysis have to be mentioned. First, the number of included studies and the sample size were small in this meta-analysis. Thus, the result of statistical analysis may be questioned. Second, for sensitivity, significantheterogeneity was found among the included studies. It is speculated that the potential sources of heterogeneity may be the differences of subjects, magnetic field intensity and MRI scan sequence. Thus, further studies need to be done to explore the sources of heterogeneity. Third, in this meta-analysis, only published literatures were included and there may be the omission of gray literatures. Thus, false-positive results may be obtained and the diagnostic performance of MRI may be exaggerated. In view of these limitations, the application of MRI diagnosis for PE must be prudentially promoted.
In conclusion, MRI is a diagnostic method of PE with the good diagnostic performance of high sensitivity and specificity, low missed diagnosis and misdiagnosis rates and strong discriminative ability. With the improvement of technology and the increase of equipment performance, MRI will have a broad application prospect in the clinical diagnosis of PE in future.

Measuring Concentrations of Vitamin C | Experiment

Vitamin C also known as ascorbic acid is synthesized by plant tissues, as well as mammals except guinea pig and primates (including man). Experiment by Lind in 1753 were the first to show the powers of vitamins when he examined that the killer disease scurvy could be prevented or rapidly cured by feeding patients fresh citrus fruits. Many foods in this world contain vitamin C.
Ascorbic acid is a powerful reducing agent giving up 2 hydrogen atoms to become dehydroascorbic acid. The usual method for the determination of ascorbic acid content is based upon its stability to reduce the dye 2-6 dichlorophenol indophenols (D.C.P.I.P) to a colourless compound. The concentration of D.C.P.I.P is set by an international standard.
The mass of ascorbic acid equivalent to 1 cm³ of D.C.P.I.P is given as 0.05 mg (International Data Standard July 1980)
RESEARCH QUESTION: What is the effect of cooking on the amount of vitamin C in foods?
HYPOTHESIS: If the cooking time for the lemon juice is longer, than the concentration of ascorbic acid contain in the lemon juice will become lower. This is because, when much time is spent to boil the lemon juice, the vitamin C will destroy and as the result it lessens the concentration of the ascorbic acid. Therefore, higher volume of solution* is needed to bleach the blue colour of the D.C.P.I.P solution.
VARIABLE: INDEPENDENT: The time period for the lemon juice to be cooked. Those lemon juices are cooked for three different time period 0 minute (fresh lemon juice), 10 min and 60 minute (1 hour).
DEPENDENT: The concentration of ascorbic acid in the lemon juice. The concentration is measured by calculating the volume of solution* used to reduce the blue colour of D.C.P.I.P to colourless. By using a burette, the mixture of lemon juice, distilled water and glacial acetic acid is titrated into the D.C.P.I.P solution. The volume is noted when the blue colour change to colourless.
CONTROL:
The volume of appropriate lemon juice used for each experiment. 4.00 cm³ of appropriate lemon juice is poured into the 100 cm³ measuring cylinder for each three experiment.
The volume of D.C.P.I.P used for every trial. By using a syringe 1 cm³ of D.C.P.I.P is being mixed with distilled water and lemon juice.
The volume of glacial acetic acid used to mix with distilled water and lemon juice. For each experiment, only 10.0 cm³ of glacial acetic acid is being poured in the solution.
APPARATUS: Glacial acetic acid
Some
Distilled water
Some
D.C.P.I.P
Some
Lemon juice
4.0 cm³ for each kind of juice
Table 2: The list of material
METHOD: Refer to the attachment.
DATA PROCESSING AND PRESENTATION QUANTITATIVE DATA: Number
Juice sample (lemon)
Trials
The volume of solution* use to reduce the blue of D.C.P.I.P to colourless, V, cm³, (±0.05 cm³)

Uncertainty for measuring cylinder = (± 0.1 cm³)
Volume of glacial acetic acid = (10.0 ± 0.1) cm³
Volume of appropriate lemon juice = (4.0 ± 0.1) cm³
Volume of D.C.P.I.P = (1.0 ± 0.1) cm³
Volume of solution* = (100.0 ± 0.5) cm³
QUALITATIVE DATA: Observation:
The colour of D.C.P.I.P changes from blue to colourless when the lemon juice is being titrated into it.
The juice is yellowish in colour and become lighter when it is diluted with acid and water.
DATA PROCESSING: The volume of solution* The volume of solution* is calculated by using the step below;
(Final volume – initial volume) cm3
For example, the volume of solution for the first trial which tested upon the fresh lemon juice:
9.50cm³ – 3.90 cm³ = (5.60 ± 0.10) cm³
The volume of solution for other trials for each appropriate lemon juice is calculated using the same method as above.
The average volume of solution* The average volume of solution is counted by dividing the volume (calculated in (a)) with 5 trials. The formula is illustrated below:
Volume for (trial 1 trial 2 trial 3 trial 4 trial 5) cm³
5
The fresh lemon juice is taken as the example for this formula.
= (5.60 8.00 5.20 6.00 5.50) cm³
5
= 30.30 cm³
5
= (6.06±0.10) cm³
The calculation for the other two appropriate lemon juices will be using the same method as shown in (2).
The concentration of ascorbic acid in each lemon juice The calculation to determine the concentration of ascorbic acid in each juice is shown below;
The mass of ascorbic acid equivalent to 1 cm3 D.C.P.I.P = 0.05 mg
Now n cm3 of the juice solution* = 1 cm3 D.C.P.I.P
So, n cm3 of the solution* = 0.05 mg ascorbic acid
Therefore, 1 cm3 of the solution* = mg ascorbic acid
Therefore, 1 cm3 of the original juice = mg ascorbic acid
Therefore, concentration of ascorbic acid in original juice
= mg/100cm3
For example, the calculation for determining the concentration of fresh lemon juice.
Average volume for solution* = 6.06 cm³
The mass of ascorbic acid equivalent to 1 cm3 D.C.P.I.P = 0.05 mg
Now 6.06 cm3 of the juice solution* = 1 cm3 D.C.P.I.P
So, 6.06 cm3 of the solution* = 0.05 mg ascorbic acid
Therefore, 1 cm3 of the solution* = mg ascorbic acid
Therefore, 1 cm3 of the original juice = mg ascorbic acid
Therefore, concentration of ascorbic acid in original juice
= mg/100cm3
= 20.63 mg/100 cm³
The calculation of concentration ascorbic acid for other appropriate lemon juice is counted using the steps in no (2) above.
The calculation of standard deviation The calculation of standard deviation for the concentration of ascorbic acid in each lemon juice is measured by using the formula below.
Δ M = ΔV1 ΔV2 ΔV3 ΔV4 ΔV5 x M
V1 V2 V3 V4 V5
ΔM = the uncertainty for the concentration of ascorbic acid in the lemon juice
M = the concentration of ascorbic acid in the lemon juice
ΔV1 = the uncertainty for the volume of D.C.P.I.P (syringe)
V1 = the volume of D.C.P.I.P (syringe)
ΔV2 = the uncertainty of the volume of glacial acetic acid (10cm³ measuring cylinder)
V2 = the volume of glacial acetic acid (10cm³ measuring cylinder)
ΔV3 = the uncertainty for the volume of appropriate lemon juice (10cm³ measuring cylinder)
V3 = the volume of appropriate lemon juice (10cm³ measuring cylinder)
ΔV4 = the uncertainty for the volume of solution* (100 cm³ measuring cylinder)
V4 = the volume of solution* (100 cm³ measuring cylinder)
ΔV5 = the uncertainty for the average volume of solution in burette
V5 = the average volume of solution in burette
An example for determining the standard deviation of the concentration of ascorbic acid in the lemon juice is shown below.
Fresh lemon juice,
Δ M = 0.1 0.1 0.1 0.5 0.10 x 20.63
1.0 10.0 4.0 100.0 6.06
= ± 3.23 mg/100 cm³
The calculation for other standard deviation will be using the same formula as above.
The tables for data processing and graph Number
The cooking time for the sample of juice (lemon)
The average volume of solution* use to reduce the blue of D.C.P.I.P to colourless, V, cm³, (±0.10 cm³)
The concentration of ascorbic acid in each lemon juice, M, mg/100 cm³
The standard deviation for the concentration of ascorbic acid in each lemon juice, M, mg/100 cm³ (±)

DISCUSSION D.C.P.I.P is used as an indicator for vitamin C. If more vitamin C or ascorbic acid is found in the food, then the rate for the D.C.P.I.P to change its blue colour will become faster.
D.C.P.I.P (blue) ascorbic acid D.C.P.I.P.H2 (colourless)
The bar graph shows the relationship between the cooking time for the juice sample and the concentration of ascorbic acid in these lemon juice, M, mg/100 cm³.
According to the bar graph, the highest concentration of ascorbic acid is in the fresh lemon juice which is 20.63 mg/100 cm³. This shows that, a fresh uncooked fruits contain a lot of vitamin C which is also known as the ascorbic acid. By observing the bar graph above, we can say that there is almost 100% of vitamin C contain in the fresh lemon juice or other fruits.
If the concentration of ascorbic acid contain in the lemon juice is higher, then less solution* is needed to undergo this titration. By referring to the Table 4, only 6.06 cm³ of solution* is required for changing the blue colour of D.C.P.I.P to colourless.
15.63 mg/100 cm³ of the concentration of ascorbic acid has been measured in the lemon juice boiled for about 10 minutes. This shows that even though the liquid is boiled for a short time period, but it has affected the vitamin C in the juice quite much.
The boiled lemon juice (1 hour) has lowest concentration of ascorbic acid which is 12.78 mg/100 cm³ and it is clearly shown by the bar graph. From this observation, we can say that, when the lemon juice is being cooked, the amount of ascorbic acid is reduced because a lot of vitamin C has been destroying while boiling the juice.
Ascorbic acid present in almost all fruits and vegetable that man eats. For example, guava, citrus fruits, spinach, broccoli and potatoes. They are best consuming when they are still fresh. However, if people still want to cook them, make sure they set the fruits and vegetable on fire less than 10 minutes. This is important in order to keep the vitamin C concentration in the fruits or vegetable which is essential for our body system.
LIMITATION AND SUGGESTION LIMITATIONS
SUGGESTIONS
The way of shaking the D.C.P.I.P in the conical flask. The D.C.P.I.P in some mixture turns to colourless faster than it should be. This has affected the mass of ascorbic acid used in the experiment.
Shake the conical flask which contains the D.C.P.I.P slowly. For each experiment, only one person is assigned to shake the D.C.P.I.P as to synchronize the force incurred onto the solution. Thus the accurate volume of ascorbic acid can be obtained during the experiment.
The solution is not well mix. When the liquid is poured into the burette, some of the lemon juice assembles at the top of the apparatus. Therefore, when it is being titrated, the concentration of ascorbic acid is not fully obtained.
Before putting the solution* into the burette, stir the distilled water, glacial acetic acid and lemon juice well by using a glass rod. The process can be done in the 100 cm³ measuring cylinder.
The colour change of D.C.P.I.P is quite difficult to be seen. Student could sometimes misinterpret the exact time when the changes of colour occur. This may lead to a fluctuation in the volume of solution* used during titration.
Placed a white tile under the conical flasks as to make it easy to see the colour change of the solution. This may help in getting the accurate volume of solution used to titrate the D.C.P.I.P.
Parallax error may occur while reading the volume of solution* in the burette. This is more complicated especially when the bubble accumulate at the surface of the solution*.
Make sure the eye is parallel to the meniscus of the solution (water). For both initial and final volume, consider the reading below the bubble. By doing so, an accurate volume may be attain
CONCLUSION Therefore as the conclusion, when longer time is spent to boil the lemon juice, then the concentration of vitamin C in that lemon juice will reduce. As the result, higher volume of solution* is needed to titrate with the D.C.P.I.P. Higher quantity of solution* is also used to discolour the blue solution of D.C.P.I.P during the experiment. Therefore, the hypothesis is supported.
*solution = appropriate lemon juice distilled water glacial acetic acid

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