Here’s What to Expect Before, During, and After an MRI


MRIs sound like a nightmare—but they don’t have to be.
MRI-Machine

Getting an MRI scan probably doesn’t top your list of ways to spend your free time, unless you like lying in tubes that make loud and mystifying noises. Can’t relate!

Unfortunately, sometimes getting an MRI (which stands for magnetic resonance imaging) is just a medically necessary evil. In that case, you’ll have to schlep over to your local radiology clinic or hospital to spend some quality time inside a machine that lets doctors see what’s up inside your body. If the thought sends shivers down your spine, there’s some good news: MRIs often aren’t as scary as they seem.

In case you’re not familiar with the test, an MRI uses a magnetic field and radio waves to make detailed pictures of your insides.

When you’re inside an MRI machine, its magnetic field temporarily realigns hydrogen atoms in your body, according to the Mayo Clinic. Radio waves make these atoms create very faint signals—and those are used to make cross-sectional images. Those images are layered on top of each other to give doctors a really good view of the inside of your body that they can see from different angles.

Doctors will often turn to an MRI when they suspect you have an injury or illness that an X-ray, CT scan, or ultrasound won’t pick up, Mina Makary, M.D., chief diagnostic radiology resident at The Ohio State University Wexner Medical Center, tells SELF. “It provides excellent anatomical detail of the soft tissues, which is helpful for the evaluation of specific conditions,” she explains.

There is a huge range of issues an MRI can spot, including disk abnormalities in your spine, joint problems, tumors in various organs like your kidneys and ovaries, structural problems in your heart, and brain injuries, according to the Mayo Clinic.

You don’t usually have to do a ton of preparation before you get an MRI.

In most cases, you’ll make an appointment to have your scan done and just show up with zero prep work, Kerry L. Thomas, M.D., a radiologist at Moffitt Cancer Center, tells SELF. But if you’re undergoing a pelvic or abdominal MRI, your doctor may ask you to avoid eating or drinking for a few hours beforehand. Skipping food and beverages for a bit will improve the image quality by causing less movement in your gastrointestinal tract, Bachir Taouli, M.D., a professor of radiology and director of body MRI at the Icahn School of Medicine at Mount Sinai, New York, tells SELF.

There are a few things that can mess with your test, which is why it’s so important to be upfront and honest about your health history.

If you have tattoos, the Mayo Clinic advises asking your doctor whether they might impact your test results, since some darker inks can contain metal. “The most important part of having an MRI is that you do not have any metal on for your scan,” Dr. Thomas says. “The machine is very a strong magnet, and metals can cause problems.”

It’s also important to tell your doctor if you’re pregnant or think you may be pregnant. Medical experts don’t understand the effects of magnetic fields on fetuses, and your doctor may recommend using an alternative test or postponing the MRI until after you give birth, the Mayo Clinic says.

Once you arrive at the appointment, you’ll need to remove all metal you might be wearing, like rings, earrings, or glasses and fill out a checklist to make sure you don’t have metal inside your body, like an artificial heart valve, pacemaker, or cochlear implants. Your doctor may also ask if you have a copper IUD (sold under the brand name ParaGard), since copper is a metal. While it’s safe to get an MRI when you have a copper IUD, the prescribing information recommends doing it at what’s known as 1.5 Tesla (the unit used to measure MRI strength), which isn’t as powerful as the 3.0 Tesla often used for MRIs, Dr. Taouli says. This is to avoid the (very minimal) chance of the magnet affecting the metal in the IUD.

Depending on why you’re having your MRI, you may need an injection of a contrasting agent beforehand.

In some cases, your doctor will want to perform an MRI with contrast, which means you’ll be injected with a contrasting agent like gadolinium right before your MRI. Gadolinium lights up when you get a scan and can help doctors get a better look at your brain, heart, and blood vessels. This can aid them in making a diagnosis of things like cancer or an inflammatory condition like multiple sclerosis, Suresh Mukherji, M.D., chairman of the department of radiology at Michigan State University, tells SELF. The American College of Radiology notes that the use of contrast agents is “not completely devoid of risk,” pointing out that some people may have side effects ranging from minor discomfort to “rare severe life-threatening situations.” According to the ACR, the adverse event rate for gadolinium-based contrast media (GBCM) ranges from 0.07 percent to 2.4 percent, which includes mild reactions (like coldness or warmth, headache, nausea) to more severe allergic-like reactions.

The ACR notes that millions of MRIs are done with contrast every year without issues. Allergic-like reactions and severe life-threatening anaphylactic reactions are uncommon, but can happen in less than 1 percent of cases, according to the ACR.

Some people also worry about after-effects. The ACR notes that residual gadolinium was recently found in the brain tissue of people who received multiple gadolinium-based contrasts in the past. The Food and Drug Administration also released a safety alert stating that the brain can retain gadolinium deposits, but also said it found no evidence that this is harmful. Ultimately, the FDA says that the benefits of an MRI with contrast exceed the potential risks.

If you’re nervous about having an MRI with contrast, talk to your doctor about why they requested this particular test and whether you have other options.

Once you change into a gown, it’s time to get into the MRI machine.

The machine will typically be long and tube-shaped with one or two open ends, though newer “open” MRI machines may not be closed on the sides. An MRI technician will ask you to lie down on a table and will often hand you a headset to put on before the actual test gets started. “Patients are given a headset to allow for communication during the MRI scan,” Dr. Taouli explains.

When it’s time for your test to begin, the technician will go behind a partition and the platform you’re lying on will move into the MRI machine. The table you’re on might move you around to allow for better imaging, but you’ll typically need to keep your body as motionless as possible during your exam. “It is critical to lie still during an MRI examination as any movement can disrupt the images being formed, and the exam will need to be repeated,” Dr. Makary says. The only exception is during a functional MRI, when the technician might ask you to perform small tasks like tapping your thumb against your fingers to see how your brain works, according to the Mayo Clinic.

It’s probably going to be loud and you might feel kind of claustrophobic, but there are some things you can do to make getting an MRI as comfortable as possible.

While there’s some variation depending on your injury or illness, MRIs can take anywhere from 15 minutes to over an hour, according to the Mayo Clinic. That’s a lot of time to be amped up with anxiety, so there are a few steps you can take to stay calm.

During your MRI, you’ll hear really loud noises like thumping and tapping as the machine goes to work. If you already know that’s going to freak you out, you can ask for earplugs. The MRI technician may also be able to play music through the headset you’re wearing, so you can ask if this is a possibility when setting up your scan. You might also want to ask if you’ll be able to use an “open” MRI machine rather than one closed at the sides, or at least one that’s newer and might be roomier than past models.

Even though the inside of newer MRI machines aren’t exactly palatial, they’re better than they used to be. Older MRI machines had ceilings that were very close to a person’s face and head, making it easy to feel claustrophobic during your scan, according to the USCF Department of Radiology & Biomedical Imaging. The tunnels in newer MRI machines are bigger and, while you still might feel a little claustrophobic, you have more space than you would have in the past.

Even better, depending on the part of your body being evaluated, you may not need to have your entire body or head inside the machine at all.

If you’d like to have other options, too, ask your doctor if you’re a candidate for sedation, anesthesia, or an anti-anxiety drug they can prescribe for you to take beforehand. You can also ask about the possibility of holding a “panic button” that you can press if you’re getting scared and need to stop the exam.

It’s worth discussing all of this with your medical team way before your appointment. This will allow you to take advantage of any accommodations possible, just in case, and also to better anticipate exactly what the process will feel like.

You really don’t need to do anything special after your scan.

You’ll simply change back into your clothes, grab your stuff, and go about your day. There also aren’t any restrictions on what you can do after the test. “Patients can resume their normal activities immediately after the MRI scan,” Dr. Taouli says. (Unless you had any drugs for sedation or anxiety, in which case you may need someone to drive you home; be sure to ask your doctor about this beforehand.)

Beyond that, you’ll just need to wait to hear from your doctor about your test results. This might feel as anxiety-provoking as getting the MRI itself, which is why it’s a good idea to ask how long it’ll take for you hear back, along with potential next steps you can expect based on their findings so you’re prepared for all outcomes.

The value of magnetic resonance imaging and ultrasonography (MRI/US)-fusion biopsy platforms in prostate cancer detection: a systematic review


Abstract

Despite limitations considering the presence, staging and aggressiveness of prostate cancer, ultrasonography (US)-guided systematic biopsies (SBs) are still the ‘gold standard’ for the diagnosis of prostate cancer. Recently, promising results have been published for targeted prostate biopsies (TBs) using magnetic resonance imaging (MRI) and ultrasonography (MRI/US)-fusion platforms. Different platforms are USA Food and Drug Administration registered and have, mostly subjective, strengths and weaknesses. To our knowledge, no systematic review exists that objectively compares prostate cancer detection rates between the different platforms available. To assess the value of the different MRI/US-fusion platforms in prostate cancer detection, we compared platform-guided TB with SB, and other ways of MRI TB (cognitive fusion or in-bore MR fusion). We performed a systematic review of well-designed prospective randomised and non-randomised trials in the English language published between 1 January 2004 and 17 February 2015, using PubMed, Embase and Cochrane Library databases. Search terms included: ‘prostate cancer’, ‘MR/ultrasound(US) fusion’ and ‘targeted biopsies’. Extraction of articles was performed by two authors (M.G. and A.A.) and were evaluated by the other authors. Randomised and non-randomised prospective clinical trials comparing TB using MRI/US-fusion platforms and SB, or other ways of TB (cognitive fusion or MR in-bore fusion) were included. In all, 11 of 1865 studies met the inclusion criteria, involving seven different fusion platforms and 2626 patients: 1119 biopsy naïve, 1433 with prior negative biopsy, 50 not mentioned (either biopsy naïve or with prior negative biopsy) and 24 on active surveillance (who were disregarded). The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of included articles. No clear advantage of MRI/US fusion-guided TBs was seen for cancer detection rates (CDRs) of all prostate cancers. However, MRI/US fusion-guided TBs tended to give higher CDRs for clinically significant prostate cancers in our analysis. Important limitations of the present systematic review include: the limited number of included studies, lack of a general definition of ‘clinically significant’ prostate cancer, the heterogeneous study population, and a reference test with low sensitivity and specificity. Today, a limited number of prospective studies have reported the CDRs of fusion platforms. Although MRI/US-fusion TB has proved its value in men with prior negative biopsies, general use of this technique in diagnosing prostate cancer should only be performed after critical consideration. Before bringing MRI/US fusion-guided TB in to general practice, there is a need for more prospective studies on prostate cancer diagnosis.

Introduction

Diagnostic tools for prostate cancer consist of DRE, serum PSA measurements, and definite diagnosis is always based on pathological evaluation of TRUS-guided systematic biopsies (SBs). However, TRUS-guided biopsy has several limitations. As 25–39% of the prostate carcinomas are iso-echoic on grey scale TRUS, biopsies cannot be limited to lesion-directed biopsies and therefore SBs have to be taken [1, 2]. Limitations of SB include the low negative predictive value (NPV) and poor correlation with pathology results after radical prostatectomy (RP) [3].

To overcome these problems, in the last decade, the focus has been on developing more accurate imaging methods for taking targeted biopsies (TBs). Research has been focused on multiparametric MRI (mpMRI), elastography, dynamic contrast-enhanced ultrasonography (DCEUS), histoscanning, and artificial neuronal network analysis (ANNA)/computerised TRUS (C-TRUS ). In general, mpMRI includes two or three MRI modalities: T2-weighted imaging , diffusion-weighted imaging (DWI), and in most cases dynamic contrast-enhancement MRI (DCE-MRI), and sometimes four, adding MR-spectroscopy. mpMRI has been reported to have a high accuracy for the detection of prostate cancer [4], and has already been recommended for patients with a persistent clinical suspicion of prostate cancer after prior negative biopsies in the European Society of Urogenital Radiology (ESUR) prostate MR guidelines 2012 [5] and in the European Association of Urology guidelines on Prostate Cancer 2014 [6].

TRUS is a non-invasive procedure used to guide the needle for taking prostate biopsies. Image fusion can combine advantages of both TRUS and mpMRI. Approaches of taking MRI-guided TBs of the prostate include ‘in-bore’ MRI-guided biopsies, cognitive fusion, and MRI/ultrasonography (MRI/US) software-based image-fusion techniques. In in-bore MRI-guided techniques, TBs are taken during real-time MRI. With fusion techniques, MRI is performed before taking US-guided TBs, using cognitive or software-based MRI–US image fusion. A higher detection rate of clinically significant disease was assessed using any of the three techniques [7]. Recently, a comparison has been made between MRI TBs and randomised TRUS-guided SBs by Van Hove et al. [8]. They concluded that no clear advantage of TBs over the current standard of SBs could be seen in biopsy naïve men, but in cases of prior negative biopsies, TBs tended to have improved prostate cancer detection rates (CDRs).

Eight fusion platforms were USA Food and Drug Administration (FDA) registered at the time this review was performed. They all require a pre-biopsy MRI for real-time TRUS fusion; however, great differences between the platforms exist. Of most importance is the difference between ‘rigid’ and ‘elastic’ registration. Often, the shape of the prostate differs significantly between MRI and TRUS imaging. Elastic methods stretch or warp one of the image datasets, so that the shapes correlate with each other. Other differences include mechanical vs manually controlled arm, patient movement compensation, and accuracy of three-dimensional modelling. To the best of our knowledge, no systematic review has been performed to compare different MRI/US-fusion platforms for taking prostate TBs.

The aim of the present review was to assess the CDRs of different MRI/US-fusion platforms for prostate cancer detection by comparing MRI/US-fusion TB to random SB and to the other MRI/US-fusion techniques, in-bore and cognitive fusion-guided TB. Only well-designed and prospective randomised and non-randomised trials were included in the review.

Patients and Methods

Eligibility Criteria

Randomised and non-randomised prospective clinical trials comparing prostate CDRs between MRI/US fusion-guided TB or another way of MRI TB, such as cognitive or in-bore MR/US-fusion, and SB were selected. Participants of any age with a clinical suspicion on prostate cancer because of high PSA level and/or abnormal DRE were considered. The primary outcome measure was (clinically significant) prostate CDRs per patient.

Study Selection

Studies were identified by searching on-line databases. A systematic literature review of PubMed, Embase and Cochrane Library was performed. The last search was conducted on 17 February 2015. The following search terms were used: prostate cancer AND ((MR/US fusion) OR (MRI/US fusion) OR (MR/ultrasound fusion) OR (MRI/ultrasound fusion) OR (ultrasound fusion) OR (targeted biopsy) OR (targeted biopsies)) with the limitations: English, humans, 01 January 2004 till 17 February 2015, full text.

Eligibility assessment was performed by two reviewers (M.G. and A.A.). Disagreements were resolved by consensus. All abstracts published before January 2004 were excluded, as in this year the first MRI/US-fusion platform was FDA registered. Articles only including patients on active surveillance were also excluded, because the objective was to assess CDRs for prostate cancer diagnosis.

Data Extraction

One review author (M.G.) extracted the following data: type of fusion platform, number and type of patients, method, comparison, outcome measures, and results, and entered the information in a data extraction sheet. All other authors checked these data and disagreements were resolved by discussion and consensus. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool [9] was used to assess the quality of included the articles.

The primary outcome measure was the prostate CDR in MRI/US fusion platform-guided TB compared with SB or another way of MRI-guided TB, such as cognitive or in-bore.

Results

Characteristics of Included Studies

In all, 2098 records were identified during the systematic literature search. After adjusting for duplicates 1865 records remained, of which 130 titles seemed relevant. Of these, 107 records were excluded because after analysing abstracts the papers did not meet the inclusion criteria. Next, the content of 23 papers were screened on relevance, and finally 11 studies met all our inclusion criteria. A flowchart of study selection is provided in Figure 1. All 11 studies finally selected were prospective non-randomised controlled trials or in-patient control studies published in English between January 2004 and February 2015. Of the 11 included studies, there were eight studies comparing transrectal MRI/US-fusion TBs with SBs and three studies comparing transperineal MRI/US-fusion TBs with SBs. Unfortunately, no study comparing MRI/US-fusion TB with in-bore TB, was detected.

Figure 1.

Study selection flowchart.

Participants

The included studies involved 2626 patients: 1119 biopsy naïve men, 1433 after prior negative biopsy, 50 not mentioned (either biopsy naïve or after prior negative biopsy) and 24 on active surveillance. Despite active surveillance being an exclusion criterion, one study including 125 patients of whom 24 patients were on active surveillance was included in the present review, because the authors presented a separate analysis for the active surveillance group, so that these men could be disregarded.

Intervention

Table 1 shows the characteristics of the 11 included studies. For the intervention, a pre-biopsy 1.5 T or 3.0 T mpMRI including at least T2-weighted imaging, DWI and DCE modalities, with or without endorectal coil, was used. MRI/US-fusion TBs were performed first in eight studies, SBs were performed first in the other three studies. The physician taking SBs was ‘blinded’ to the MRI images in five studies. In two studies, the physician taking the SBs was not blinded to the MRI images, and in the other four studies, blinding was not mentioned.

Table 1. Characteristics of the 11 included studies
Study Fusion platform Sample size, n Patients MRI MRI/US fusion-guided TB Comparison
Strength, T Sequences Endorectal coil Score Patients with positive MRI, % Route Mean no. of cores TB first Standard test No. of cores Blinded to MRI
  1. AS, active surveillence; NM, not mentioned; TR, tranrectal; TP, transperineal; T1, T1-weighted imaging; T2, T2-weighted imaging.
Borkowetz et al. [10] BioJet 263 Biopsy naive (68), prior negative biopsy (195) 3.0 T1, T2, DWI, DCE No PI-RADS 100.0 TP 8.9 Yes TR SB 12 No
Delongchamps et al. [14] Virtual Navigator and Urostation 391 Biopsy naive 1.5 T2, DWI, DCE Yes NIH 40.7 TR 3.6 No TR SB 10–12 NM
Fiard et al. [17] Urostation 30 Biopsy naive (13), prior negative biopsy (17) 3.0 T2, DWI, DCE No PI-RADS 66.7 TR 1.5 No TR SB 12 NM
Junker et al. [21] Logiq 9 50 Biopsy naive (# NM), prior negative biopsy (# NM) 3.0 T2, DWI, DCE No PI-RADS 100.0 TR 4.5 Yes TR SB 10 Yes
Kuru et al. [19] BiopSee 347 Biopsy naive (177), prior negative biopsy (170) 3.0 T1, T2, DWI, DCE, spectroscopy No NIH 72.9 TP 4.0 Yes TP SB 12–36 NM
Mozer et al. [15] Urostation 152 Biopsy naive 1.5 T2, DWI, DCE No Likert 100.0 TR 2.0 No TR SB 12 Yes
Rastinehad et al. [11] UroNav 105 Biopsy naive (35), prior negative biopsy (70) 3.0 T2, DWI, DCE No NIH 100.0 TR 3.9 Yes TR SB 12 Yes
Salami et al. [12] UroNav 140 Prior negative biopsy 3.0 T2, DWI, DCE Yes Likert 100.0 TR NM Yes TR SB 12 NM
Shoji et al. [16] BioJet 20 Biopsy naive 1.5 T1, T2, DWI, DCE No PI-RADS 100.0 TP NM Yes TP SB 12 No
Siddiqui et al. [18] UroNav 1003 Biopsy naive (196), prior negative biopsy (807) 3.0 T2, DWI, DCE Yes NIH 100.0 TR 5.4 Yes TRSB 12 Yes
Wysock et al. [13] Artemis 125 Biopsy naive (67), prior negative biopsy (34), AS (24) 3.0 T2, DWI, DCE No Likert 100.0 TR 2.8 Yes TR VE-TB and SB 12 Yes

The mpMRI lesions were scored using the Prostate Imaging-Reporting And Data System (PI-RADS), Likert score or National Institutes of Health (NIH) score. MRI/US-fusion TBs were taken transrectally in eight studies and transperineally in three studies, with the mean number of cores taken ranging from 1.5 to 8.9 per patient.

Outcomes

In all studies, the primary or secondary outcome assessed was the CDR of all prostate cancer and/or the CDR of clinically significant prostate cancer. When clinically significant prostate cancer based on prostate biopsies was mentioned, it was defined as:

  1. Epstein criteria: any Gleason score ≥7 or Gleason score 6 with a lesion volume of >0.2 mL (Borkowetz et al. [10], Rastinehad et al. [11], Salami et al. [12], Wysock et al. [13]);
  2. All cancers excluding microfocal cancer, defined as a single core with <5 mm of Gleason score 6 cancer (Delongchamps et al. [14]);
  3. At least one core with a Gleason score 3 + 4 or 6 with a maximum cancer core length of ≥4 mm (Mozer et al. [15], Shoji et al. [16]);
  4. Total serum PSA level of >10 ng/mL or clinical stage ≥T2b/or Gleason score ≥4 or total cancer length on biopsy of ≥10 mm (Fiard et al. [17]).

Siddiqui et al. [18] did not mention clinically significant prostate cancer, but made a separate analysis of high-grade prostate cancer, defined as Gleason score ≥4 + 3.

Kuru et al. [19] did not mention clinically significant prostate cancer either, but made separate analyses for low vs high/intermediate prostate cancers, defined according to the National Comprehensive Cancer Network (NCCN) guidelines [20].

Risk of Bias Within Studies

For a transparent rating of bias and applicability of diagnostic accuracy studies, the QUADAS-2 tool was used to assess the quality of included articles (Table 2). In all studies, patient selection and index test were defined as low risk of bias. Risk of bias concerning the reference test was assessed high in all included studies because of the low accuracy of prostate SBs. Applicability of the index test was scored as a high risk of bias in all studies, because of the different fusion platforms and strategies for MRI/US fusion-guided prostate TBs. The item ‘flow and timing’ was assessed as high risk of bias in a few studies, because time from mpMRI until prostate TB was not mentioned.

Table 2. QUADAS-2 results
Study Judgments on bias Judgments on applicability
Patient selection Index test Reference standard Flow and timing Patient selection Index test Reference standard
Borkowetz et al. [10] Low risk Low risk High risk High risk Low risk High risk Low risk
Delongchamps et al. [14] Low risk Low risk High risk High risk Low risk High risk Low risk
Fiard et al. [17] Low risk Low risk High risk High risk Low risk High risk Low risk
Junker et al. [21] Low risk Low risk High risk High risk Low risk High risk Low risk
Kuru et al. [19] Low risk Low risk High risk High risk Low risk High risk High risk
Mozer et al. [15] Low risk Low risk High risk Low risk Low risk High risk Low risk
Rastinehad et al. [11] Low risk Low risk High risk High risk Low risk High risk Low risk
Salami et al. [12] Low risk Low risk High risk High risk Low risk High risk Low risk
Shoji et al. [16] Low risk Low risk High risk High risk Low risk High risk Low risk
Siddiqui et al. [18] Low risk Low risk High risk Low risk Low risk High risk Low risk
Wysock et al. [13] Low risk Low risk High risk High risk Low risk High risk Low risk

Results of Individual Studies

The CDR of all prostate cancers and when mentioned, clinically significant prostate cancers, per patient of individual studies are presented in Table 3. A sub-analysis with the CDRs for low- vs moderate- to high-risk lesions, graded on mpMRI is presented in Table 4.

Table 3. Prostate CDR in trials comparing MRI/US fusion-guided prostate TB with other ways of TB or SB
Study Platform MRI/US-fusion TB VE-TB SB
Total CDR, n/N (%) CDR of clinically significant prostate cancer, n/N (%) Total CDR, n/N (%) CDR of clinically significant prostate cancer, n/N (%) Total CDR, n/N (%) CDR of clinically significant prostate cancer, n/N (%)
Borkowetz et al. [10] BioJet 116/263 (44.1) 91/263 (34.6)
94/263 (35.7) 75/263 (28.5)
Delongchamps et al. [14] Virtual Navigator and Urostation 40/54 (74.1) 55/127 (43.3)
40/54 (74.1) 43/127 (33.9)
62/78 (79.5) 60/131 (45.8)
56/78 (71.8) 45/131 (34.4)
62/82 (75.6) 44/133 (33.1)
58/82 (70.7) 35/133 (26.3)
Fiard et al. [17] Urostation 82/152 (53.9) 86/152 (56.6)
66/152 (43.4) 56/152 (36.8)
Junker et al. [21] Logiq 9 23/50 (46.0) 18/50 (36.0)
Kuru et al. [19] BiopSee 103/253 (40.7) 175/347 (50.4)
Mozer et al. [15] Urostation 82/152 (53.9) 86/152 (56.6)
66/152 (43.4) 56/152 (36.8)
Rastinehad et al. [11] UroNav 53/105 (50.5) 51/105 (48.8)
47/105 (44.8) 34/105 (32.4)
Salami et al. [12] UroNav 73/140 (52.1) 68/140 (48.6)
67/140 (47.9) 43/140 (30.7)
Shoji et al. [16] BioJet 14/20 (70.0) 8/20 (40.0)
Siddiqui et al. [18] UroNav 461/1003 (46.0) 469/1003 (46.8)
Wysock et al. [13] Artemis 34/101 (33.7) 31/101 (30.7)
Table 4. Sub-analysis of CDRs per patient in low- vs moderate- to high-risk prostate cancers, graded on mpMRI
Study CDR total, n/N (%) CDR TB, n/N (%) CDR SB, n/N (%)
Low-risk lesions on mpMRI High-risk lesions on mpMRI Low-risk lesions on mpMRI High-risk lesions on mpMRI Low-risk lesions on mpMRI High-risk lesions on mpMRI
  1. MR-TB, MRI/US fusion platform-guided TB; NM, not mentioned; *per lesion, not per patient.
Borkowetz et al. [10] 65/269 (24.2) 77/185 (41.6) NM NM NM NM
Delongchamps et al. [14] NM NM NM NM NM NM
Fiard et al. [17] NM NM NM NM NM NM
Junker et al. [21] NM NM 2/7 (28.6)* 29/50 (58.0)* NM NM
Kuru et al. [19] 114/243 (46.9) 100/149 (67.0) NM NM NM NM
Mozer et al. [15] NM NM 9/54 (16.7) 73/98 (74.5) NM NM
Rastinehad et al. [11] 19/40 (47.5) 47/65 (72.3) 13/40 (32.5) 40/65 (61.5) 14/40 (35.0) 37/65 (56.9)
Salami et al. [12] 31/68 (45.6) 60/72 (83.3) 18/68 (26.5) 55/72 (76.4) 25/68 (36.8) 43/72 (59.7)
Shoji et al. [16] NM NM NM NM NM NM
Siddiqui et al. [18] NM NM NM NM NM NM
Wysock et al. [13] NM NM MR-TB: 15/74 (20.3)

VE-TB: 9/74 (12.2)

MR-TB: 30/51 (58.8)

VE-TB: 30/51 (58.8)

NM NM

Syntheses of Results

In all, 11 studies were included in this systematic review, using Virtual Navigator (one study, [14]), Urostation (three studies [14, 15, 17]), Logiq 9 (one study [21]), UroNav (three studies [11, 12, 18]), Artemis (one study [13]), BiopSee (one study [19]) and BioJet (two studies, [10, 16]).

The CDRs per patient were available for all 11 trials, including 2626 patients. Excluding the 24 patients on active surveillance results for 2602 patients were available for analysis.

Borkowetz et al. [10] compared transperineal MRI/US-fusion TB, using the BioJet platform, to transrectal SB in 263 patients. The overall CDR was 52%. For both the CDRs of all prostate cancers and clinically significant prostate cancer, MRI/US-fusion TB detected significantly more cancer than SB (44.1% vs 34.6% and 35.7% vs 28.5% respectively).

Delongchamps et al. [14] made a comparison of the accuracy of visually estimated TB (VE-TB) vs MRI/US-guided TB using a rigid (Virtual Navigator) or elastic (Urostation) approach, all compared to standard 12-core SB. In all, 391 biopsy naïve men were included and divided into three groups (VE-TB, rigid fusion, elastic fusion). In conclusion, MRI/US-guided TB performed significantly better (CDRs of 79.5% and 75.6% for Virtual Navigator and Urostation, respectively) than SB (ranging from 33.1% to 45.8% in all three groups), whereas VE-TB did not (74.1%).

Fiard et al. [17] included 30 patients with a clinical suspicion of prostate cancer, 17 men with prior negative biopsy and 13 biopsy naïve men. Suspicious area(s) were found on MRI in 20 cases. MRI/US-fusion TBs were performed using the Urostation. The CDRs of MRI/US-guided TB and SB were 55.0% and 43.3%, no further statistical analysis was made. The NPVs of SB and TB were 94% and 85%.

Junker et al. [21] analysed 50 patients using the Logiq 9 fusion system. The CDRs of TB and SB were 46% and 36%, resulting in a sensitivity of 69.2% for SB (18/26) and 88.5% for TB (23/26), respectively.

Kuru et al. [19] made a comparison between transrectal US-guided transperineal-fusion TB, using the BiopSee platform, and transperineal SB. The CDRs of all prostate cancers were equal in both SB and TB (50.4% and 50.6% respectively). However, there was a difference in the CDR in favour of TB for clinically significant prostate cancers according to the NCCN guidelines (41.1% for TB vs 38.0% for SB).

Mozer et al. [15] included 152 biopsy naïve men. The CDRs of all prostate cancers for TB and SB were 53.9% and 56.6%, respectively, but there was a statistical significant difference in the CDRs of clinically significant prostate cancer between the two protocols in favour of TB (43.3% vs 36.8%).

The value of the UroNav platform was examined by Rastinehad et al. [11]. In all, 105 patients were included in their trial. The CDRs of all prostate cancers by TB vs SB were 50.5% and 48.8%, respectively. For clinically significant disease, the CDRs were 44.8% and 32.4%, respectively, which was a statistically significant difference.

The UroNav platform was also used by Salami et al. [12] in 140 patients with prior negative biopsy. The CDRs of MRI/US fusion-guided TB was 52.1% and 47.9% for all prostate cancers and clinically significant prostate cancers, respectively. The CDR of standard 12-core SB was 48.6% and 30.7% for all prostate cancers and clinically significant prostate cancers, respectively. The CDRs of MRI/US-guided TB and SB were not statistically significantly different, but MRI/US fusion-guided TBs detected more clinically significant prostate cancer when compared with SBs.

Shoji et al. [16] made a comparison between transperineal TB and SB, using the BioJet platform; 20 patients were included in their analysis, with CDRs for TB and SB of 70.0% vs 40.0%.

Siddiqui et al. [18] included 1003 patients in their prospective cohort study. SBs and TBs, using the UroNav platform, were taken. The CDRs of all prostate cancers by TB vs SB were not different (46.0% and 46.8%, respectively). However, TB diagnosed 30% more high-risk cancers than SB (17.2% vs 12.2%, respectively).

Wysock et al. [13] included 125 patients, of whom 67 were biopsy naïve, 34 had prior negative biopsy and 24 were on active surveillance. Overall, the CDR per patient was 23.2% and 19.2% for MRI/US-guided TB and VE-TB, respectively, with the difference being statistically insignificant. For the 101 biopsy naïve patients or with prior negative biopsy only, the total CDR was 33.7% vs 30.7% for the MRI/US-guided TBs vs VE-TBs. Pooled TBs (MRI/US-guided TB and VE-TB together) compared with SB in 67 biopsy naïve men showed a lower overall CDR (40.3% vs 55.2%) and less Gleason score 6 disease (7.5% vs 22.4%), but detected an equivalent number of Gleason score ≥7 disease (32.8% vs 32.8%).

A sub-analysis was made of low- vs moderate- to high-risk lesions, graded on mpMRI.

Moderate- to high-risk lesions include 4–5 lesions on a 5-point scale and 2–3 lesions on a 3-point scale. Four studies gave an overall sub-analysis, with CDRs for low-risk lesions ranging from 24.2% to 47.5% and for moderate- to high-risk lesions from 41.6% to 83.3%.

Five studies made a sub-analysis for TB of low- vs moderate- to high-risk lesions, but only two of these studies also gave a sub-analysis of SB. Within these two studies, including 245 patients, the CDRs in low-risk lesions were almost equal in TB and SB (CDRs of 26.5–32.5% in TB and 35.0–36.8% in SB) with a difference in CDRs in moderate- to high-risk lesions in favour of TB (CDRs 61.5–76.4% in TB and 56.9–59.7% in SB).

Discussion

In the present review, the value of different MRI/US platforms in prostate cancer detection was assessed by comparing the CDRs of MRI/US-fusion TBs with SB, and to other MRI/US-fusion techniques, such as in-bore and VE-TB. Most importantly, seven of eight FDA registered MRI/US-fusion platforms have been validated using prospective studies comparing CDRs of MRI/US-guided TBs with VE-TBs or SBs in the diagnosis of prostate cancer.

To date, the diagnosis of prostate cancer has had substantial limitations. First of all, biopsy Gleason score upgrading after pathological assessment of RP specimens shows a discrepancy between grading in TRUS-guided SBs and RP specimens [22]. Because of this discrepancy and due to the lack of large cohort studies, a good prediction of clinically significant disease is hampered.

Secondly, there is an ongoing debate about the definition of ‘clinically significant’ disease and in addition, with the introduction of TB, the question arises as to whether the same definition for clinically significant prostate cancer should be maintained for cores obtained with SB and TB. To overcome over-diagnosis and overtreatment, it is important to limit the diagnosis of clinically insignificant prostate cancer. There is some evidence that the criteria for clinically significant prostate cancer suggested by Epstein et al. [23] have a high likelihood for identifying organ-confined disease but not clinically insignificant disease [24, 25].

Therefore, the most ideal development in prostate cancer diagnosis would be a test with high positive predictive values (PPVs) and NPVs for clinically significant disease. A recently published systematic review by Fütterer et al. [26] showed NPVs and PPVs for clinically significant prostate cancer with mpMRI ranging from 63% to 98% and 34% to 68%, respectively. The overall sensitivity and specificity of mpMRI reported are promising, but the additional value of DCE-MRI is still questioned [27]. Also, of great importance is the evidence that there are statistically significant histological differences between detected and missed prostate cancers on mpMRI [28], with detected prostate cancers on mpMRI showing more clinically significant features. The CDR in patients with prior negative biopsy with in-bore MR-guided TB varies from 52% to 59% [29, 30]. TB especially may play a role in improving anterior prostate cancer detection [31].

In our present analysis, no clear advantage of MRI/US fusion-guided TBs could be seen for the CDRs of all prostate cancers, but MRI/US fusion-guided TBs tended to give a higher CDR for clinically significant prostate cancers. This is consistent with the results of the systematic reviews of Valerio et al. [32] and Van Hove et al. [8]. It would be interesting to see whether there is a difference between CDRs in low- vs high-risk lesions on mpMRI when comparing TB with SB. Unfortunately, only two studies made this sub-analysis, showing contradictory results. While the study of Rastinehad et al. [11] showed no clear difference between TB and SB, the study of Salami et al. [12] tended to give a higher CDR in high-risk lesions with TB.

There are some general limitations in assessing the value of MRI/US-fusion TBs. First of all, the range in CDRs at SB suggests that there is a difference in the quality of taking biopsies. Furthermore, it seems plausible that the strength of the MRI magnet and the use of an endorectal or pelvic coils determine the quality of MR images and the experience of the radiologist and physician performing the biopsy determines the quality of the biopsy cores, which determines the CDR. However, this has not been properly studied. In most of the included studies, men with negative mpMRI were disregarded, which creates selection bias and makes the results less applicable to clinical practice. And although direct visualisation of the biopsy needle inside the suspicious area is technically possible [33], in common practice, it is almost never used.

The present systematic review has several limitations. First of all, 11 studies met our inclusion criteria, including 2626 patients. Because of this limited number of included studies, no statement can be made about the difference in the CDRs between the different fusion platforms. Another important limitation is the lack of a general definition of clinically significant prostate cancer. As shown in our present results, in the 11 included articles, four different definitions are being used. The aim of our present systematic review was to assess the CDRs in MRI/US-fusion TB vs SB in the diagnosis of prostate cancer. Patients included in the original studies are heterogeneous, containing biopsy naïve men and men with one, two or sometimes more prior negative biopsies. Because previous studies show that the CDR is dependent on biopsy session number [34, 35], the included studies are difficult to compare. On the other hand, these results are applicable to clinical practice. A general limitation of studies using SB as a reference test is that it lacks accuracy, i.e. has low sensitivity and specificity [3]. It is used because a good gold standard, such as RP, is unethical to use.

Conclusion

Although MRI/US-fusion TB has proved its value in men with prior negative biopsies, general use of this technique in the diagnosis of prostate cancer should only be performed after critical consideration because in our present analysis, no clear advantage of MRI/US fusion-guided TB could be found for CDRs of all prostate cancers; however, MRI/US fusion-guided TBs tended to give a higher CDR for clinically significant prostate cancers. Before bringing MRI/US fusion-guided TB in to general practice, there is a need for more prospective studies on its effectiveness for prostate cancer diagnosis.

Parallel to our research question about CDRs, is the important question of whether SB can be omitted, because this will have an impact on clinical practice. There is also a need for more research into how many prostate cancers are missed by TB, and their clinical relevance. Moreover, individual quality of taking prostate biopsies is an under-reported problem that causes bias.

Acknowledgements

The present systemic review was undertaken with a research grant from Astellas Pharma Netherlands B.V. Astellas has not influenced the content of this manuscript.

Conflicts of Interest

None disclosed.

Abbreviations

CDR
cancer detection rate
DCE
dynamic contrast enhanced
FDA
USA Food and Drug Administration
mpMRI
multiparametric MRI
NCCN
National Comprehensive Cancer Network
NIH
National Institutes of Health
PI-RADS
Prostate Imaging-Reporting And Data System
(N)(P)PV
(negative) (positive) predictive value
QUADAS
Quality Assessment of Diagnostic Accuracy Studies
RP
radical prostatectomy
SB
systematic biopsy
(VE-)TB
(visually estimated) targeted biopsy

2014 Top Stories in Cardiology: Cardiac Imaging.


In assembling the top stories of 2014 in the field of cardiac imaging, we have focused on the major modalities of noninvasive imaging—echocardiography, nuclear cardiology, cardiac magnetic resonance imaging (CMR), and cardiac computed tomographic (CCT) imaging.

Echocardiography

The management of patients with severe mitral regurgitation due to myxomatous degeneration of the valve, particularly if asymptomatic, remains vexing. Naji and colleagues1 reported on exercise echocardiographic and clinical data in almost 900 patients with myxomatous mitral regurgitation, the majority of whom were asymptomatic. Patients were followed for a composite outcome for an average of over 6 years. Significant predictors of adverse outcomes included percent of age-/sex-predicted metabolic equivalents, heart rate recovery, resting right ventricular systolic pressure, atrial fibrillation, and LV ejection fraction. The importance of this paper lies not only in the large population with long-term follow-up, but also with the incorporation of exercise parameters into the usual clinical data, which had not been done before in such a large population. In the absence of randomized trials addressing timing of mitral valve surgery for asymptomatic severe mitral regurgitation, which are unlikely to be performed, this type of observational data set will inform guidelines and practice patterns.

Nuclear Cardiology

Almost 10 years ago, the American College of Cardiology published the first of a series of papers on the appropriate use of medical testing, originally called “Appropriateness Criteria,” now referred to as “Appropriate Use Criteria” (AUC). The goal of these recommendations is to optimize the efficiency and value of cardiac testing, based as much as possible on the published literature but also incorporating critical expert opinion. Recommendations are grouped by common clinical indications, and are categorized as “appropriate,” “may be appropriate” (formerly “uncertain”), or “rarely appropriate” (formerly “inappropriate”). Studies categorized as rarely appropriate are generally thought to be low-yield, in low-risk populations as an example. While AUC documents have been published for all common cardiac imaging tests and also for disease states such as stable ischemic heart disease or heart failure, there exists almost no literature validating the AUC categories in a prospective way against clinical outcomes. In this important paper, Doukky and colleagues2 report on over 1500 outpatients who were clinically referred for SPECT myocardial perfusion imaging. The studies were classified based on the 2009 AUC for SPECT myocardial perfusion imaging into two categories as appropriate/uncertain or as inappropriate. Patients were followed for an average of over 2 years for adverse events. Among the studies categorized as being of appropriate/uncertain indication, the SPECT results showed the usual prognostic value, in that an abnormal study was associated with a higher risk for adverse events compared with a normal study. However, among the SPECT studies characterized as inappropriate, there was not demonstrable prognostic association. To some degree, this was a result of the very low event rate among those with inappropriate studies, in turn related to the very low prevalence of abnormal studies. Nonetheless, these data are the first to examine the AUC recommendations in terms of association with outcomes, and validate the recommendations of the AUC documents. The importance of this paper lies in the fact that, within the next few years, payors including CMS will be mandating incorporation of AUC into the stream of test-ordering behavior. Having well-validated criteria is a critical element in the widespread acceptance of this approach.

Cardiac MR Imaging

Several relatively small studies have suggested that the presence and/or extent of late gadolinium hyperenhancement (LGE) on CMR imaging in patients with hypertrophic cardiomyopathy is associated with the risk for adverse events or with markers of adverse events. In this largest study to date,3 the authors assembled almost 1300 patients with hypertrophic cardiomyopathy from several centers around the world who had CMR imaging and were followed for a median of over 3 years. There was a significant association between the extent of LGE and risk for sudden death events. Among patients without established risk factors for sudden death, the extent of LGE was associated with sudden death risk, and, among those without LGE, risk was very low. The importance of this data set is that it more clearly establishes the role of CMR imaging in the prediction of sudden death risk in patients with hypertrophic cardiomyopathy. For those in whom the ICD decision may be uncertain on the basis of the usual clinical risk factors, the presence or absence of a certain mass of LGE on CMR imaging can tip the scales one way or the other on that critical decision point. For patients without any of the established risk factors, the presence and extent of LGE may drive consideration for an ICD that might not otherwise have been entertained. This study population is much larger with longer follow-up than all previous studies, allowing much more statistical power in analysis.

Cardiac CT Imaging

The technology of cardiac CT angiography has evolved substantially over the last decade, and, while the focus of much of the literature has been to recapitulate and expand the application of this modality in the same way as invasive angiography has been done, more recently, increasing attention has been on the evaluation of “non-obstructive” coronary artery disease (CAD). This can be imaged more routinely with contemporary CT techniques. In this paper, Bittencourt and colleagues4 report on over 3000 patients who had CT angiography whose scans were evaluated for the presence and extent of obstructive as well as non-obstructive CAD, and who were followed for a median of over 3 years for the occurrence of cardiovascular death or nonfatal myocardial infarction. The expected relation of obstructive CAD to events was seen, but, of great interest, those patients with extensive non-obstructive CAD had a risk for events that was similar to that in patents with less extensive obstructive CAD. Non-obstructive plaque extent added incremental information to risk stratification. These data are important for advancing the possibility of incorporating information on extent of imaged plaque into risk assessments, which may, in the future, help guide treatment decisions, or decisions regarding intensity of risk-factor management.

Conclusions

While the mature imaging modalities of echocardiography and nuclear cardiology have long had published data sets involving thousands of patients with sophisticated statistical analyses, the studies cited above suggest that the more recently evolved modalities of cardiac MR and cardiac CT have also reached a similar point regarding the rigor of prognostic data sets and publications. As always, finer gradations of risk assessment and stratification do not necessarily translate into enhanced management for patients, and must be tested separately and not simply be assumed.

2014 Top Stories in Cardiology: Cardiac Imaging


In assembling the top stories of 2014 in the field of cardiac imaging, we have focused on the major modalities of noninvasive imaging—echocardiography, nuclear cardiology, cardiac magnetic resonance imaging (CMR), and cardiac computed tomographic (CCT) imaging.

Echocardiography

The management of patients with severe mitral regurgitation due to myxomatous degeneration of the valve, particularly if asymptomatic, remains vexing. Naji and colleagues1 reported on exercise echocardiographic and clinical data in almost 900 patients with myxomatous mitral regurgitation, the majority of whom were asymptomatic. Patients were followed for a composite outcome for an average of over 6 years. Significant predictors of adverse outcomes included percent of age-/sex-predicted metabolic equivalents, heart rate recovery, resting right ventricular systolic pressure, atrial fibrillation, and LV ejection fraction. The importance of this paper lies not only in the large population with long-term follow-up, but also with the incorporation of exercise parameters into the usual clinical data, which had not been done before in such a large population. In the absence of randomized trials addressing timing of mitral valve surgery for asymptomatic severe mitral regurgitation, which are unlikely to be performed, this type of observational data set will inform guidelines and practice patterns.

Nuclear Cardiology

Almost 10 years ago, the American College of Cardiology published the first of a series of papers on the appropriate use of medical testing, originally called “Appropriateness Criteria,” now referred to as “Appropriate Use Criteria” (AUC). The goal of these recommendations is to optimize the efficiency and value of cardiac testing, based as much as possible on the published literature but also incorporating critical expert opinion. Recommendations are grouped by common clinical indications, and are categorized as “appropriate,” “may be appropriate” (formerly “uncertain”), or “rarely appropriate” (formerly “inappropriate”). Studies categorized as rarely appropriate are generally thought to be low-yield, in low-risk populations as an example. While AUC documents have been published for all common cardiac imaging tests and also for disease states such as stable ischemic heart disease or heart failure, there exists almost no literature validating the AUC categories in a prospective way against clinical outcomes. In this important paper, Doukky and colleagues2 report on over 1500 outpatients who were clinically referred for SPECT myocardial perfusion imaging. The studies were classified based on the 2009 AUC for SPECT myocardial perfusion imaging into two categories as appropriate/uncertain or as inappropriate. Patients were followed for an average of over 2 years for adverse events. Among the studies categorized as being of appropriate/uncertain indication, the SPECT results showed the usual prognostic value, in that an abnormal study was associated with a higher risk for adverse events compared with a normal study. However, among the SPECT studies characterized as inappropriate, there was not demonstrable prognostic association. To some degree, this was a result of the very low event rate among those with inappropriate studies, in turn related to the very low prevalence of abnormal studies. Nonetheless, these data are the first to examine the AUC recommendations in terms of association with outcomes, and validate the recommendations of the AUC documents. The importance of this paper lies in the fact that, within the next few years, payors including CMS will be mandating incorporation of AUC into the stream of test-ordering behavior. Having well-validated criteria is a critical element in the widespread acceptance of this approach.

Cardiac MR Imaging

Several relatively small studies have suggested that the presence and/or extent of late gadolinium hyperenhancement (LGE) on CMR imaging in patients with hypertrophic cardiomyopathy is associated with the risk for adverse events or with markers of adverse events. In this largest study to date,3 the authors assembled almost 1300 patients with hypertrophic cardiomyopathy from several centers around the world who had CMR imaging and were followed for a median of over 3 years. There was a significant association between the extent of LGE and risk for sudden death events. Among patients without established risk factors for sudden death, the extent of LGE was associated with sudden death risk, and, among those without LGE, risk was very low. The importance of this data set is that it more clearly establishes the role of CMR imaging in the prediction of sudden death risk in patients with hypertrophic cardiomyopathy. For those in whom the ICD decision may be uncertain on the basis of the usual clinical risk factors, the presence or absence of a certain mass of LGE on CMR imaging can tip the scales one way or the other on that critical decision point. For patients without any of the established risk factors, the presence and extent of LGE may drive consideration for an ICD that might not otherwise have been entertained. This study population is much larger with longer follow-up than all previous studies, allowing much more statistical power in analysis.

Cardiac CT Imaging

The technology of cardiac CT angiography has evolved substantially over the last decade, and, while the focus of much of the literature has been to recapitulate and expand the application of this modality in the same way as invasive angiography has been done, more recently, increasing attention has been on the evaluation of “non-obstructive” coronary artery disease (CAD). This can be imaged more routinely with contemporary CT techniques. In this paper, Bittencourt and colleagues4 report on over 3000 patients who had CT angiography whose scans were evaluated for the presence and extent of obstructive as well as non-obstructive CAD, and who were followed for a median of over 3 years for the occurrence of cardiovascular death or nonfatal myocardial infarction. The expected relation of obstructive CAD to events was seen, but, of great interest, those patients with extensive non-obstructive CAD had a risk for events that was similar to that in patents with less extensive obstructive CAD. Non-obstructive plaque extent added incremental information to risk stratification. These data are important for advancing the possibility of incorporating information on extent of imaged plaque into risk assessments, which may, in the future, help guide treatment decisions, or decisions regarding intensity of risk-factor management.

Conclusions

While the mature imaging modalities of echocardiography and nuclear cardiology have long had published data sets involving thousands of patients with sophisticated statistical analyses, the studies cited above suggest that the more recently evolved modalities of cardiac MR and cardiac CT have also reached a similar point regarding the rigor of prognostic data sets and publications. As always, finer gradations of risk assessment and stratification do not necessarily translate into enhanced management for patients, and must be tested separately and not simply be assumed.

MRI May Cause Pain and Complications in Patients with Cochlear Implants


Undergoing magnetic resonance imaging may be painful for patients with cochlear implants, even when safety precautions are followed, according to a small study in JAMA Otolaryngology—Head & Neck Surgery.

Researchers retrospectively studied 18 patients with cochlear implants who underwent MRI. Only 13 completed the MRI. The other five couldn’t finish it because of severe pain, even though their heads were wrapped in elastic gauze as recommended by guidelines. The implant’s internal magnet was displaced in one of these patients. Another patient required surgery to have the magnet removed and reinserted. Patient complications were not restricted to brain MRIs.

Artifacts were observed in images of patients who underwent brain MRIs.

The authors conclude: “Prior to an MRI scan, patients with [cochlear implants] must fully understand not only the potential complications but also the potential discomforts that they may experience during the scan. Appropriate sedation and head positioning can alleviate patient discomfort or pain during MRI scans.”

– See more at: http://www.jwatch.org/fw109559/2014/11/21/mri-may-cause-pain-and-complications-patients-with?query=pfw#sthash.91HNIAi4.dpuf

Human Neural Stem Cells Become Neurons in Monkey Brains.


A team of scientists based in Korea and Canada who transplanted human neural stem cells (hNSCs) into the brains of nonhuman primates (NHPs) report that the hNSCs had differentiated into neurons at 24 months and did not cause tumors. The study is scheduled to be published in Cell Transplantation.

Breakthrough: Human Neural Stem Cells Become Neurons in Monkey Brains

The hNSCs were labeled with magnetic nanoparticles to enable them to be followed by magnetic resonance imaging. The researchers, who did not use immunosuppressants, claim their study is the first to evaluate and show the long-term survival and differentiation of hNSCs without the need for immunosuppression.

“None of the grafted hNSCs were bromodeoxyuridine (BrdU)-positive in the monkey brain indicating that hNSCs did not replicate in the NHP brain and did not cause tumor-formation,” write the investigators in an unedited, available-online copy of the manuscript. “This study serves as a proof-of-principle study to provide evidence that human NSCs transplanted in NHP brain could survive and differentiate into neurons in the absence of immunosuppression, and also serves as a preliminary study in our scheduled preclinical studies of human NSC transplantation in NHP stroke models.”

The researchers maintain that hNSCs could be a key a source for cell replacement and gene transfer for the treatment of Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, spinal cord injury, and stroke.

“Stroke is the fourth major cause of death in the U.S. behind heart failure, cancer, and lower respiratory disease,” said study co-author Seung U. Kim, Ph.D., of the University of British Columbia Hospital’s department of neurology. “While tissue plasminogen activator (tPA) treatment within three hours after a stroke has shown good outcomes, stem cell therapy has the potential to address the treatment needs of those stroke patients for whom tPA treatment was unavailable or did not help.”

Dr. Kim and colleagues injected hNSCs into the frontal lobe and the putamen of the monkey brain because they are included in the middle cerebral artery (MCA) territory, which is the main target in the development of the ischemic lesion in animal stroke models. “Thus, research on survival and differentiation of hNSCs in the MCA territory should provide more meaningful information to cell transplantation in the MCA occlusion stroke model,” he explained.

The researchers said that they chose NSCs for transplantation because the existence of multipotent NSCs “has been known in developing rodents and in the human brain with the properties of indefinite growth and multipotent potential to differentiate” into the three major CNS cell types (neurons, astrocytes, and oligodendrocytes).

Researchers film early concussion damage, describe brain’s response to injury.


There is more than meets the eye following even a mild traumatic brain injury. While the brain may appear to be intact, new findings reported in Nature suggest that the brain’s protective coverings may feel the brunt of the impact.

Using a newly developed mouse trauma model, senior author Dorian McGavern, Ph.D., scientist at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, watched specific cells mount an  to the injury and try to prevent more widespread damage. Notably, additional findings suggest a similar immune response may occur in patients with mild head injury.

In this study, researchers also discovered that certain molecules, when applied directly to the mouse skull, can bypass the brain’s protective barriers and enter the brain. The findings suggested that, in the mouse trauma model, one of those molecules may reduce effects of .

Although concussions are common, not much is known about the effects of this type of damage. As part of this study, Lawrence Latour, Ph.D., a scientist from NINDS and the Center for Neuroscience and Regenerative Medicine, examined individuals who had recently suffered a concussion but whose initial scans did not reveal any physical damage to brain tissue. After administering a commonly used dye during MRI scans, Latour and his colleagues saw it leaking into the meninges, the outer covers of the brain, in 49 percent of 142 patients with concussion.

To determine what happens following this mild type of injury, researchers in Dr. McGavern’s lab developed a new model of brain trauma in mice.

“In our mice, there was leakage from blood vessels right underneath the skull bone at the site of injury, similar to the type of effect we saw in almost half of our patients who had mild . We are using this mouse model to look at meningeal trauma and how that spreads more deeply into the brain over time,” said Dr. McGavern.

Dr. McGavern and his colleagues also discovered that the intact skull bone was porous enough to allow small molecules to get through to the brain. They showed that smaller molecules reached the brain faster and to a greater extent than larger ones. “It was surprising to discover that all these protective barriers the brain has may not be concrete. You can get something to pass through them,” said Dr. McGavern.

The researchers found that applying glutathione (an antioxidant that is normally found in our cells) directly on the skull surface after brain injury reduced the amount of  by 67 percent. When the researchers applied glutathione three hours after injury, cell death was reduced by 51 percent. “This idea that we have a time window within which to work, potentially up to three hours, is exciting and may be clinically important,” said Dr. McGavern.

Glutathione works by decreasing levels of reactive oxygen species (ROS) molecules that damage cells. In this study, high levels of ROS were observed at the trauma site right after the physical brain injury occurred. The massive flood of ROS set up a sequence of events that led to cell death in the brain, but glutathione was able to prevent many of those effects.

In addition, using a powerful microscopic technique, the researchers filmed what was happening just beneath the skull surface within five minutes of injury. They captured never-before-seen details of how the brain responds to traumatic injury and how it mobilizes to defend itself.

Initially, they saw cell death in the meninges and at the glial limitans (a very thin barrier at the surface of the brain that is the last line of defense against dangerous molecules). Cell death in the underlying brain tissue did not occur until 9-12 hours after injury. “You have death in the lining first and then this penetrates into the brain tissue later. The goal of therapies for brain injury is to protect the ,” said Dr. McGavern.

Almost immediately after head injury, the glial limitans can break down and develop holes, providing a way for potentially harmful molecules to get into the brain. The researchers observed microglia (immune cells that act as first responders in the brain against dangerous substances) quickly moving up to the brain surface, plugging up the holes.

Findings from Dr. McGavern’s lab indicate that microglia do this in two ways. According to Dr. McGavern, “If the astrocytes, the cells that make up the glial limitans, are still there, microglia will come up to ‘caulk’ the barrier and plug up gaps between individual astrocytes. If an astrocyte dies, that results in a larger space in the glial limitans, so the microglia will change shape, expand into a fat jellyfish-like structure and try to plug up that hole. These reactions, which have never been seen before in living brains, help secure the barrier and prevent toxic substances from getting into the brain.”

Studies have suggested that immune responses in the brain can often lead to severe damage. Remarkably, the findings in this study show that the inflammatory response in a model is actually beneficial during the first 9-12 hours after injury.

Mild traumatic brain injuries are a growing public health concern. According to a report from the Centers of Disease Control and Prevention, in 2009 at least 2.4 million people suffered a traumatic injury and 75 percent of those injuries were mild. This study provides insight into the damage that occurs following head trauma and identifies potential therapeutic targets, such as antioxidants, for reducing the damaging effects.

TB vaccine ‘could help prevent MS’


MRI brain scan showing multiple sclerosis lesions


Related Stories

An anti-tuberculosis vaccine could prevent multiple sclerosis, early research suggests.

A small-scale study by researchers at the Sapienza University of Rome has raised hopes that the disease can be warded off when early symptoms appear.

More research is needed before the BCG vaccine can be trialled on MS patients.

The MS Society said the chance to take a safe and effective preventative treatment after a first MS-like attack would be a huge step forward.

MS is a disease affecting nerves in the brain and spinal cord, causing problems with muscle movement, balance and vision.

Early signs include numbness, vision difficulties or problems with balance.

BCG vaccine

  • Bacillus Calmette-Guerin (BCG) is a live vaccine made up of a weakened strain of Mycobacterium bovisa bacterium that causes tuberculosis (TB) in cattle
  • The bacteria are altered so that they do not cause a TB infection, but stimulate the body’s immune system to make it resistant to the disease
  • The vaccine has existed for 80 years and is one of the most widely used of all current vaccines, reaching more than 80% of newborns and infants in countries where it is part of the national childhood immunisation programme

About half of people with a first episode of symptoms go on to develop MS within two years, while 10% have no more problems.

In the study, published in the journalNeurology, Italian researchers gave 33 people who had early signs of MS an injection of BCG vaccine.

The other 40 individuals in the study were given a placebo.

After five years, 30% of those who received the placebo had not developed MS, compared with 58% of those vaccinated.

“These results are promising, but much more research needs to be done to learn more about the safety and long-term effects of this live vaccine,” said study leader Dr Giovanni Ristori.

“Doctors should not start using this vaccine to treat MS or clinically isolated syndrome.”

Dr Susan Kohlhaas, head of biomedical research at the MS Society, said it was a small but interesting study.

“It’s really encouraging to see positive results from this small trial, but they’ll need validating in larger and longer-term studies before we know if the BCG vaccination can reduce the risk of someone developing MS.

“Ultimately, the chance to take a safe and effective preventative treatment after a first MS-like attack would be a huge step forward.”

The findings add weight to a theory that exposure to infections early in life might reduce the risk of diseases such as MS by stimulating the body’s immune system.

Dr Dennis Bourdette, of Oregon Health and Science University in Portland, US, said the research suggested “BCG could prove to be a ‘safe, inexpensive, and handy’ treatment for MS”.

He wrote in an accompanying editorial in Neurology: “The theory is that exposure to certain infections early in life might reduce the risk of these diseases by inducing the body to develop a protective immunity.”

FDA Approves Implantable Neurostimulator for Epilepsy.


The US Food and Drug Administration (FDA) today approved an implantable neurostimulator to reduce the frequency of seizures in patients with epilepsy whose condition is not successfully managed with medication.

The device, called the RNS System (Neuropace, Inc), detects abnormal electrical activity and delivers a remedial dose of electricity before the patient experiences seizures. It contrasts with neurostimulators for other conditions that provide continuous or scheduled stimulation.

The RNS System is implanted inside the skull under the scalp. Its 1 or 2 electrodes are situated near the patient’s seizure focus or foci in the brain.

The FDA based its decision on a clinical trial involving 191 patients with drug-resistant epilepsy who received the implanted device. However, the device was turned on in only half the patients. After 3 months, patients with activated neurostimulators experienced almost a median 34% reduction in the average number of seizures per month. For patients with unactivated devices, the median reduction was 19%. Twenty-nine percent of patients with activated devices had at least a 50% reduction in the overall number of seizures, compared with 27% with turned-off devices.

In February, a 13-member FDA advisory panel recommended approval of the RNS System. The majority of panelists found that the device beneficial, and that the benefits outweighed the risks. There was unanimous agreement that the RNS System was safe.

Implant site infection and premature battery depletion were the most common adverse events reported during the clinical trials.

The FDA cautioned that patients with the RNS System must avoid MRI procedures, diathermy procedures, electroconvulsive therapy, and transcranial magnetic stimulation.

“The energy created from these procedures can be sent through the neurostimulator and cause permanent brain damage, even if the device is turned off,” the agency said in a news release.

Is it right to waste helium on party balloons?


The US has been selling off its helium reserve, established in the 1920s to provide gas for airships – but even so, shortages have been occurring.

Some scientists believe a finite resource that could one day run out should not be used for party balloons.

balloons

In the universe as a whole, it is one of the commonest elements, second only to hydrogen in its abundance. On Earth it is relatively rare, and the only element that escapes gravity and leaks away into space.

“All of the other elements we’ve scattered around the globe, maybe we can go digging in garbage dumps to get them back,” says chemist Andrea Sella, of University College London (UCL).

“But helium is unique. When it’s gone it is lost to us forever.”

Helium has the lowest boiling point of any element, at -269C, just a few degrees above absolute zero (-273C).

“We’re going to be looking back and thinking, I can’t believe people just used to fill up their balloons with it, when it’s so precious and unique,” says Cambridge University chemist Peter Wothers, who has called for the end to helium-filled party balloons.

“It is something we need to think about.”

That would mean an end to the old party favourite of breathing in helium from a balloon, and then talking in a high-pitched voices – a result of helium’s fast-moving molecules. But maybe this would be no bad thing, as it can cause dizziness, headaches and even death.

The gas, which is formed by the decay of radioactive rocks in the earth’s crust, accumulates in natural gas deposits and is collected as a by-product of the gas industry.

The United States is currently the world’s biggest supplier, with the bulk of it stored near Amarillo, Texas, in the national helium reserve – which alone accounts for 35% of the world’s current supply.

This was set up in 1925 as a strategic store for supplying gas to US airships, while after World War Two it provided coolant for missiles and rockets for the military and Nasa.

US airship USS Shenandoah, the first helium-filled rigid airship, 1923USS Shenandoah, the world’s first helium-filled rigid airship

But since the mid-1990s, with growing civilian demand for helium in the manufacture of semi-conductors and for MRI scanners, among other things, the US has been clawing back the cost of storing the gas by gradually selling it off on the open market.

Despite this, the price of helium has doubled over the past 10 years.

Scare stories about this or that resource running out are a commonplace of doomsayers – but this autumn, the world got a taste of what a helium shortage could mean.

US semiconductor manufacturers knew that under the terms of a 1996 law, the US helium reserve was legally obliged to turn off the tap last month.

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